gebhart/patrepeval huggingface dataset:
Endostatin Associates with Lipid Rafts and Induces Reorganization of the Actin Cytoskeleton via Down-regulation of RhoA Activity (2003)

Endostatin, the C-terminal fragment of collagen XVIII, is a potent inhibitor of angiogenesis. Observations that endostatin inhibits endothelial cell migration and induces disassembly of the actin cytoskeleton provide putative cellular mechanisms for this effect. To understand the mechanisms of endostatin-induced intracellular signaling, we analyzed the association of recombinant endostatin with endothelial cell lipid rafts and the roles of its heparin- and integrin-binding properties in this interaction. We observed that a fraction of cell surface-bound endostatin partitioned in low density membrane raft fractions together with caveolin-1. Heparinase treatment of cells prevented the recruitment of endostatin to the lipid rafts but did not affect the association of endostatin with the non-raft fraction, whereas preincubation of endostatin with soluble alpha5beta1 integrin prevented the association of endostatin with the endothelial cell membrane. Endostatin treatment induced recruitment of alpha5beta1 integrin into the raft fraction via a heparan sulfate proteoglycan-dependent mechanism. Subsequently, through alpha5beta1 integrin, heparan sulfate, and lipid raft-mediated interactions, endostatin induced Src-dependent activation of p190RhoGAP with concomitant decrease in RhoA activity and disassembly of actin stress fibers and focal adhesions. These observations provide a cell biological mechanism, which plausibly explains the anti-angiogenic mechanisms of endostatin in vivo.
Ein wasserlösliches Prodrug von Taxol mit der Fähigkeit zur Selbstorganisation (1994)

In vitro und in vivo besser wirksam gegen Tumore als die Stammverbindung Taxol – das ist Taxol‐2′‐MPA 1 . Dieses Derivat ist darüber hinaus noch wasserlöslich, womit die bei der Formulierung von Taxol auftretenden Komplikationen vermieden werden können. magnified image
Gene organisation determines evolution of function in the chicken MHC (1999)

Some years ago, we used our data for class I genes, proteins and peptide-binding specificities to develop the hypothesis that the chicken B-F/B-L region represents a "minimal essential MHC". In this view, the B locus contains the classical (highly expressed and polymorphic) class I alpha and class II beta multigene families, which are reduced to one or two members, with many other genes moved away or deleted from the chicken genome altogether. We found that a single dominantly expressed class I gene determines the immune response to certain infectious pathogens, due to peptide-binding specificity and cell-surface expression level. This stands in stark contrast to well-studied mammals like humans and mice, in which every haplotype is more-or-less responsive to every pathogen and vaccine, presumably due to the multigene family of MHC molecules present. In order to approach the basis for a single dominantly expressed class I molecule, we have sequenced a portion of the B complex and examined the location and polymorphism of the class I (B-F) alpha, TAP and class II (B-L) beta genes. The region is remarkably compact and simple, with many of the genes expected from the MHC of mammals absent, including LMP, class II alpha and DO genes as well as most class III region genes. However, unexpected genes were present, including tapasin and putative natural killer receptor genes. The region is also organised differently from mammals, with the TAPs in between the class I genes, the tapasin gene in between the class II (B-L) beta genes, and the C4 gene outside of the class I alpha and class II beta genes. The close proximity of TAP and class I alpha genes leads to the possibility of co-evolution, which can drive the use of a single dominantly expressed class I molecule with peptide-binding specificity like the TAP molecule. There is also a single dominantly expressed class II beta gene, but the reason for this is not yet clear. Finally, the presence of the C4 gene outside of the classical class I alpha and class II beta genes suggests the possibility that this organisation was ancestral, although a number of models of organisation and evolution are still possible, given the presence of the Rfp-Y region with non-classical class I alpha and class II beta genes as well as the presence of multigene families of B-G and rRNA genes.
Lack of effect of exogenous insulin-like growth factor-I (IGF-I) on chick embryo growth rate (1990)

International audience
Sequence Analysis of the P and C Protein Genes of Human Parainfluenza Virus Type 3: Patterns of Amino Acid Sequence Homology Among Paramyxovirus Proteins (1986)

The complete nucleotide sequence of the P + C mRNA of human parainfluenza virus type 3 (PF3) was determined by sequencing cDNA, viral genomic RNA and mRNA. The P + C mRNA is 2009 nucleotides in length, exclusive of poly(A), and contains two overlapping open reading frames (ORFs). The P + C mRNA encodes two proteins, the 602 amino acid nucleocapsid phosphoprotein P and the 199 amino acid non-structural protein C. Peptide mapping confirmed that the two proteins are unrelated. Hybrid-arrest translation experiments assigned each of the two proteins to its respective ORF. These studies showed that the coding strategy of the PF3 P + C mRNA is similar to that of Sendai virus. Amino acid sequence alignment showed that the P and C proteins of PF3 and Sendai virus represent homologous pairs. However, these homologies are represented by high contents of accepted amino acid substitutions and by similarity in hydropathy profiles rather than by high contents of exact amino acid matches. Homology with the P and C proteins of measles, canine distemper and respiratory syncytial viruses was at the threshold of significance. The patterns of amino acid sequence homology among the paramyxovirus HN, F, NP, P and C proteins are compared.
Early lung cancer with lepidic pattern (2014)

The validity and clinical importance of the novel concept of ADC precursor lesions and LPA have been confirmed by clinical, radiological, morphological, and molecular data. Thereby, it has evolved into a valuable tool to aid in clinical decision-making.
Discovery of three genes specifically expressed in human prostate by expressed sequence tag database analysis (1998)

A procedure is described to discover genes that are specifically expressed in human prostate. The procedure involves searching the expressed sequence tag (EST) database for genes that have many related EST sequences from human prostate cDNA libraries but none or few from nonprostate human libraries. The selected candidate EST clones were tested by RNA dot blots to examine tissue specificity and by Northern blots to examine the transcript size of the corresponding mRNA. The computer analysis identified 15 promising genes that were previously unidentified. When seven of these were examined in an RNA hybridization experiment, three were found to be prostate specific. The genes identified could be useful in the targeted therapy of prostate cancer. The procedure can easily be applied to discover genes specifically expressed in other organs or tumors.
A single base change altered the regulation of the Waxy gene at the posttranscriptional level during the domestication of rice (1998)

The rice waxy (wx) locus has two functional alleles, Wxa and Wxb, which are defined by a large difference in the amount of the gene product, called Wx protein, that accumulates in mature seeds. To elucidate the molecular mechanism underlying this difference and to identify the base change causing the alteration of the regulation of the Wx gene during rice evolution, we determined the nucleotide sequences of the regulatory region of Wx alleles and analyzed their function in a transient assay system using rice protoplasts. All Wxa alleles from Oryza sativa Indica, O. rufipogon, and O. glaberrima have a normal sequence of GT at the 5' splice junction of the first intron, representing a high expression level of the Wx transcripts in the endosperm and a high beta-glucuronidase (GUS) activity in protoplasts. On the other hand, Wxb alleles from two strains of O. sativa Japonica have TT at the 5' splice junction, representing a low expression level of the mature transcripts and a low GUS activity. Northern blot analysis also indicated that a larger transcript, consisting of the unspliced first intron, is closely correlated with the function of the Wxb allele. These results suggest that a single base change at the 5' splice junction causes inefficient splicing and, as a result, reduces the level of mature transcript and the GUS activity in the Wxb allele. The Wxb allele in O. saativa Japonica may have been differentiated from the Wxa allele of O. rufipogon, its wild progenitor, by this mutation, and, therefore, a single base change that has altered the regulation of the Wx gene at the posttranscriptional level probably occurred during the domestication of rice.
Common Misconceptions in Chest Radiology (2003)

Dr. Baron is Professor of Radiology, Emory University School of Medicine, 1364 Clifton Road NE, Atlanta, GA 30322; [email protected]. The author has disclosed that he has no significant relationships with or financial interests in any commercial organizations pertaining to this educational activity.
Physical association between the high-affinity IgG receptor (Fc gamma RI) and the gamma subunit of the high-affinity IgE receptor (Fc epsilon RI gamma). (1993)

To investigate the structural basis of transmembrane signaling via the high-affinity IgG receptor (Fc gamma RI), the identity of Fc gamma RI-associated proteins in THP-1 human monocytic cells was examined. Anti-Fc gamma RI monoclonal antibody (mAb) 197 immunoprecipitates from 125I-labeled THP-1 cells solubilized in 1% digitonin buffer were found to contain a protein migrating at 12 kDa on reduction. This protein comigrated with the 12-kDa protein precipitated by the anti-high-affinity IgE receptor gamma chain (Fc epsilon RI gamma) mAb 4D8. Similarly, a 70-kDa band immunoprecipitated by mAb 4D8 comigrated with the 70-kDa protein band corresponding to Fc gamma RI in mAb 197 immunoprecipitates. On two-dimensional nonreducing-reducing gel analysis, the 12-kDa protein present in both mAb 197 and mAb 4D8 immunoprecipitates migrated as a disulfide-linked homodimer. Analysis of 1% Nonidet P-40 eluates of the digitonin immunoprecipitates under reducing conditions demonstrated the presence of a 12-kDa band in the mAb 197 immunoprecipitate that could be reprecipitated with mAb 4D8. Conversely, a 70-kDa band in the mAb 4D8 immunoprecipitate could be reprecipitated with mAb 197. Similar to these findings, both mAb 197 and mAb 4D8 precipitated a 12-kDa disulfide-linked homodimeric protein from digitonin lysates of 125I-labeled human neutrophils after induction of Fc gamma RI expression with interferon gamma but not from unstimulated neutrophils. Northern blot analysis confirmed the presence of Fc epsilon RI gamma mRNA in interferon gamma-induced human neutrophils. We conclude that Fc epsilon RI gamma, a member of a family of proteins implicated in transmembrane signaling via immune recognition receptors, associates with Fc gamma RI in human cells.
On the Shared Control of an EMG-Controlled Prosthetic Hand: Analysis of User–Prosthesis Interaction (2008)

An anthropomorphic underactuated prosthetic hand, endowed with position and force sensors and controlled by means of myoelectric commands, is used to perform experiments of hierarchical shared control. Three different hierarchical control strategies combined with a vibrotactile feedback system have been developed and tested by able-bodied subjects through grasping tasks used in activities of daily living (ADLs). The first goal is to find a good tradeoff between good grasping capabilities and low attention required by the user to complete grasping tasks, without addressing advanced algorithm for electromyographic processing. The second goal is to understand whether a vibrotactile feedback system is subjectively or objectively useful and how it changes users' performance. Experiments showed that users were able to successfully operate the device in the three control strategies, and that the grasp success increased with more interactive control. Practice has proven that when too much effort is required, subjects do not do their best, preferring, instead, a less-interactive control strategy. Moreover, the experiments showed that when grasping tasks are performed under visual control, the enhanced proprioception offered by a vibrotactile system is practically not exploited. Nevertheless, in subjective opinion, feedback seems to be quite important.
Extensive telomere repeat arrays in mouse are hypervariable (1990)

In this study we have analysed mouse telomeres by Pulsed Field Gel Electrophoresis (PFGE). A number of specific restriction fragments hybridising to a (TTA-GGG)4 probe in the size range 50-150kb can be detected. These fragments are devoid of sites for most restriction enzymes suggesting that they comprise simple repeats; we argue that most of these are likely to be (TTAGGG)n. Each discrete fragment corresponds to the telomere of an individual chromosome and segregates as a Mendelian character. However, new size variants are being generated in the germ line at very high rates such that inbred mice are heterozygous at all telomeres analysable. In addition we show that specific small (approximately 4-12kb) fragments can be cleaved within some terminal arrays by the restriction enzyme MnII which recognises 5'(N7)GAGG3'. Like the complete telomere-repeat arrays (TRA's) these fragments form new variants at high rates and possibly by the same process. We speculate on the mechanisms that may be involved.
THE EDINBURGH DETECTIVE (Book) (2002)

Humans have used serotonergic hallucinogens (i.e. psychedelics) for spiritual, ceremonial, and recreational purposes for thousands of years, but their administration as part of a structured therapeutic intervention is still a relatively novel practice within Western medical and psychological frameworks. In the mid-20<sup>th</sup> century, considerable advances were made in developing therapeutic approaches integrating administration of low (<i>psycholytic</i>) and high (<i>psychedelic</i>) doses of serotonergic hallucinogens for treatment of a variety of conditions, often incorporating psychoanalytic concepts prevalent at that time. This work contributed seminal insights regarding how these substances may be employed with efficacy and safety in targeted therapeutic interventions, including the importance of optimizing set (frame of mind) and setting (therapeutic environment). More recently, clinical and pharmacological research has revisited the effects and therapeutic potential of psychedelics utilizing a variety of approaches. The current article provides an overview of past and present models of psychedelic therapy, and discusses important considerations for future interventions incorporating the use of psychedelics in research and clinical practice.
Solution Structure and Backbone Dynamics of the TGFβ Type II Receptor Extracellular Domain, (2003)

Isoforms of transforming growth factor beta (TGFbeta) are 25 kDa homodimeric polypeptides that signal by binding and bringing together two related, functionally distinct cell surface receptors designated as TbetaR1 and TbetaR2. Here, we report the solution structure of the 13.8 kDa extracellular domain of human TbetaR2 (ecTbetaR2) as calculated from N(N)-H(N), C(alpha)-H(alpha), and C(alpha)-C(O) residual dipolar coupling restraints in conjunction with NOE distance, dihedral angle, and scalar coupling restraints. Comparison of the free ecTbetaR2 solution structure with the TGFbeta3-bound ecTbetaR2 crystal structure reveals backbone conformations that superimpose with RMSDs of 1.0 A over the regions of regular secondary structure and 1.4 A overall. The differences in structure fall mainly in loop regions that are either poorly defined by the available NMR data or are involved in crystal contacts. The noted similarities between the NMR structure of the free form and the crystal structure of the TGFbeta-bound form are also consistent with the close correspondence, 0.16 A RMSD for regions of secondary structure and 0.51 A RMSD overall, for the crystal structure of free ecTbetaR2 as compared to the crystal structure of TGFbeta3-bound ecTbetaR2. Despite the apparent similarities between the free and the bound forms, there appears to be small but significant differences in structure involving the interfacial contact region of the receptor. Measurements of backbone (15)N relaxation times and interpretation of these by the model-free formalism with axial diffusional anisotropy further reveal significant ms to micros time scale motions centered about two of the conserved disulfide bonds and in several residues that comprise the TGFbeta binding surface. Together, these observations indicate that binding likely occurs through a mechanism with a small component of induced fit character, whereby flexibility within the receptor facilitates the transition to the TGFbeta-bound state.
Opioids intrinsically inhibit the genesis of mouse cerebellar granule neuron precursors in vitro: differential impact of μ and δ receptor activation on proliferation and neurite elongation (2000)

Although opioids are known to affect neurogenesis in vivo, it is uncertain the extent to which opioids directly or indirectly affect the proliferation, differentiation or death of neuronal precursors. To address these questions, the intrinsic role of the opioid system in neurogenesis was systematically explored in cerebellar external granular layer (EGL) neuronal precursors isolated from postnatal mice and maintained in vitro. Isolated neuronal precursors expressed proenkephalin-derived peptides, as well as specific mu and delta, but negligible kappa, opioid receptors. The developmental effects of opioids were highly selective. Morphine-induced mu receptor activation inhibited DNA synthesis, while a preferential delta2-receptor agonist ([D-Ala2]-deltorphin II) or Met-enkephalin, but not the delta1 agonist [D-Pen2, D-Pen5]-enkephalin, inhibited differentiation within the same neuronal population. If similar patterns occur in the developing cerebellum, spatiotemporal differences in endogenous mu and delta opioid ligand-receptor interactions may coordinate distinct aspects of granule neuron maturation. The data additionally suggest that perinatal exposure to opiate drugs of abuse directly interfere with cerebellar maturation by disrupting normal opioid signalling and inhibiting the proliferation of granule neuron precursors.
DMM-Net: Differentiable Mask-Matching Network for Video Object Segmentation (2019)

In this paper, we propose the differentiable mask-matching network (DMM-Net) for solving the video object segmentation problem where the initial object masks are provided. Relying on the Mask R-CNN backbone, we extract mask proposals per frame and formulate the matching between object templates and proposals at one time step as a linear assignment problem where the cost matrix is predicted by a CNN. We propose a differentiable matching layer by unrolling a projected gradient descent algorithm in which the projection exploits the Dykstra's algorithm. We prove that under mild conditions, the matching is guaranteed to converge to the optimum. In practice, it performs similarly to the Hungarian algorithm during inference. Meanwhile, we can back-propagate through it to learn the cost matrix. After matching, a refinement head is leveraged to improve the quality of the matched mask. Our DMM-Net achieves competitive results on the largest video object segmentation dataset YouTube-VOS. On DAVIS 2017, DMM-Net achieves the best performance without online learning on the first frames. Without any fine-tuning, DMM-Net performs comparably to state-of-the-art methods on SegTrack v2 dataset. At last, our matching layer is very simple to implement; we attach the PyTorch code ($&lt;50$ lines) in the supplementary material. Our code is released at https://github.com/ZENGXH/DMM_Net.
A Targetable Androgen Receptor–Positive Breast Cancer Subtype Hidden Among the Triple-Negative Cancers (2014)

AR is the most commonly expressed hormone receptor among all breast carcinomas, with a prevalence of 25% to 75% among TNBCs. Therefore, we strongly support the routine assessment of AR in TNBC, and preferably in all breast carcinomas.
The NF-κB-inducing Kinase Induces PC12 Cell Differentiation and Prevents Apoptosis (2000)

NF-kappa B has been implicated in the survival and differentiation of PC12 cells. In this study, we examined the effect of the NF-kappa B-inducing kinase (NIK) on these processes. When inducibly expressed in PC12 cells, a kinase-proficient but not -deficient form of NIK promoted neurite process formation and mediated anti-apoptotic signaling. As expected, NIK expression led to I kappa B kinase activation and induced nuclear translocation of NF-kappa B. However, NIK-induced neurite outgrowth was only partially blocked by concomitant expression of a nondegradable form of I kappa B alpha that completely blocks NF-kappa B induction. In search of additional signaling pathways activated by NIK, we now demonstrate that NIK activates MEK1 phosphorylation and induces the Erk1/Erk2 MAPK pathway. Treatment of PC12 cells with PD98059, a MEK1 inhibitor, potently blocked neurite process formation; however, a dominantly interfering mutant of the upstream Shc adapter failed to alter this response. These findings reveal a new function for NIK as a MEK1-dependent activator of the MAPK pathway and implicate both the I kappa B kinase and MAPK signaling cascades in NIK-induced differentiation of PC12 cells.
Generation of a Novel HLA Class I Transgenic Mouse Model Carrying a Knock-in Mutation at the β2-Microglobulin Locus (2016)

We generated a series of monochain HLA class I knock-in (KI) mouse strains, in which a chimeric HLA class I molecule (α1/α2 domain of HLA-A*0201, HLA-A*0301, HLA-A*2402, or HLA-A*3101 and α3 domain of H-2D<sup>b</sup>) was covalently linked with 15 aa to human β<sub>2</sub>-microglobulin (β<sub>2</sub>m) and introduced into the endogenous mouse β<sub>2</sub>m locus. In homozygous KI mice, mouse β<sub>2</sub>m gene disruption resulted in loss of the endogenous H-2 class I molecules and reduction in the peripheral CD8<sup>+</sup> T cell population that was partially restored by monochain HLA class I expression. A gene dosage-dependent expression of HLA, similar to that in human PBMCs, was detected in heterozygous and homozygous HLA KI mice. Upon vaccination with various virus epitopes, HLA-restricted, epitope-specific CTLs were induced in HLA KI mice, similar to the response in the commonly used HLA transgenic mice. Importantly, the CTL responses induced in heterozygous KI mice were similar to those in homozygous KI mice. These results suggest that coexpression of H-2 class I does not affect HLA-restricted CTL responses in HLA KI mice, which differs from the situation reported for monochain HLA Tg × β2m<sup>-/-</sup> mice. Furthermore, we generated double KI mice harboring two different HLA (HLA-A*2402 and HLA-A*0301) KI alleles, which showed a CTL response against both HLA-A24 and HLA-A3 epitopes when immunized with a mixture of both peptides. These results indicated that this HLA class I KI mouse model provides powerful research tools not only for the study of HLA class I-restricted CTL responses, but also for preclinical vaccine evaluation.