gebhart/patrepeval huggingface dataset:
Over my fake body: body ownership illusions for studying the multisensory basis of own-body perception (2015)

Which is my body and how do I distinguish it from the bodies of others, or from objects in the surrounding environment? The perception of our own body and more particularly our sense of body ownership is taken for granted. Nevertheless, experimental findings from body ownership illusions (BOIs), show that under specific multisensory conditions, we can experience artificial body parts or fake bodies as our own body parts or body, respectively. The aim of the present paper is to discuss how and why BOIs are induced. We review several experimental findings concerning the spatial, temporal, and semantic principles of crossmodal stimuli that have been applied to induce BOIs. On the basis of these principles, we discuss theoretical approaches concerning the underlying mechanism of BOIs. We propose a conceptualization based on Bayesian causal inference for addressing how our nervous system could infer whether an object belongs to our own body, using multisensory, sensorimotor, and semantic information, and we discuss how this can account for several experimental findings. Finally, we point to neural network models as an implementational framework within which the computational problem behind BOIs could be addressed in the future.
The diagnostic importance of CEA and CA 19-9 for the early diagnosis of pancreatic carcinoma. (2001)

With the progression of the pancreatic carcinoma, serum CEA level and the specificity of CEA were elevated similar to that of CA 19-9. However, the elevation of CEA specificity when compared with the control group was lower than the specificity of the CA 19-9 and the sensitivity of CA 19-9 was superior to that of CEA for pancreatic carcinoma. The level of CA 19-9 was increased with the development of early pancreatic cancer and this elevation steadily continued with the progression of the cancer.
Myosin Vb Is Required for Trafficking of the Cystic Fibrosis Transmembrane Conductance Regulator in Rab11a-specific Apical Recycling Endosomes in Polarized Human Airway Epithelial Cells (2007)

Cystic fibrosis transmembrane conductance regulator (CFTR)-mediated Cl(-) secretion across fluid-transporting epithelia is regulated, in part, by modulating the number of CFTR Cl(-) channels in the plasma membrane by adjusting CFTR endocytosis and recycling. However, the mechanisms that regulate CFTR recycling in airway epithelial cells remain unknown, at least in part, because the recycling itineraries of CFTR in these cells are incompletely understood. In a previous study, we demonstrated that CFTR undergoes trafficking in Rab11a-specific apical recycling endosomes in human airway epithelial cells. Myosin Vb is a plus-end-directed, actin-based mechanoenzyme that facilitates protein trafficking in Rab11a-specific recycling vesicles in several cell model systems. There are no published studies examining the role of myosin Vb in airway epithelial cells. Thus, the goal of this study was to determine whether myosin Vb facilitates CFTR recycling in polarized human airway epithelial cells. Endogenous CFTR formed a complex with endogenous myosin Vb and Rab11a. Silencing myosin Vb by RNA-mediated interference decreased the expression of wild-type CFTR and DeltaF508-CFTR in the apical membrane and decreased CFTR-mediated Cl(-) secretion across polarized human airway epithelial cells. A recombinant tail domain fragment of myosin Vb attenuated the plasma membrane expression of CFTR by arresting CFTR recycling. The dominant-negative effect was dependent on the ability of the myosin Vb tail fragment to interact with Rab11a. Taken together, these data indicate that myosin Vb is required for CFTR recycling in Rab11a-specific apical recycling endosomes in polarized human airway epithelial cells.
Antiangiogenic activity of the HSP90 inhibitor ganetespib in pancreatic cancer models (2013)

Heat shock protein 90 (HSP90) has a central role in the regulation of transcriptional factors that modulate angiogenesis and growth. Ganetespib (G) is a functional inhibitor of HSP90 being studied in a broad range of clinical trials. We tested the hypothesis that functional inhibition of HSP90 by G can inhibit angiogenesis and growth in vitro and in vivo models of pancreatic cancer. PANC‐1, and HPAC cell lines were treated with vehicle or G (50nM) for 24 h and lysates were analyzed by Western blot. Egg CAM and matrigel plug assays were performed to quantify the effects of G on angiogenesis. Efficacy of G (100mg/kg) was assessed in mice bearing HPAC and ASPC‐1 xenograft. Western blot analyses demonstrated a significant reduction in intracellular HIF‐1á and VEGF protein levels in PANC‐1 and HPAC cells treated with G. Results from ELISA assays showed that G reduced VEGF secretion in the culture medium from both pancreatic lines. G treatment reduced angiogenesis compared to vehicle in all three models. Animals with human pancreatic tumor xenografts treated with G had significant tumor growth delay and inhibition of angiogenesis. The preclinical data demonstrates that G can inhibit pancreatic cancer growth and angiogenesis, suggesting that targeting HSP90 is a rational new approach to pancreatic cancer therapy to be explored in clinical trials.
Effect of Adenovirus-Mediated Heat Shock Protein Expression and Oncolysis in Combination with Low-Dose Cyclophosphamide Treatment on Antitumor Immune Responses (2006)

Heat shock proteins such as gp96 have the ability to chaperone peptides and activate antigen-presenting cells. In this study, we tested whether adenovirus-mediated overexpression of secreted or membrane-associated forms of gp96 in tumor cells would stimulate an antitumor immune response. Studies were carried out in C57Bl/6 mice bearing aggressively growing s.c. tumors derived from syngeneic TC-1 cells, a cell line that expresses HPV16 E6 and E7 proteins. We found that secreted gp96 can induce protective and therapeutic antitumor immune responses. Our data also indicate that the antitumor effect of sgp96 expression seems to be limited by the induction of suppressive regulatory T cells (Treg). TC-1 tumor transplantation increased the number of splenic and tumor-infiltrating Tregs. Importantly, treatment of mice with low-dose cyclophosphamide decreased the number of Tregs and enhanced the immunostimulatory effect of sgp96 expression. We also tested whether an oncolytic vector (Ad.IR-E1A/TRAIL), that is able to induce tumor cell apoptosis and, potentially, release cryptic tumor epitopes in immunogenic form, could stimulate antitumor immune responses. Although tumor cells infected ex vivo with Ad.IR-E1A/TRAIL had no antitumor effect when used as a vaccine alone, the additional treatment with low-dose cyclophosphamide resulted in the elimination of pre-established tumors. This study gives a rationale for testing approaches that suppress Tregs in combination with oncolytic or immunostimulatory vectors.
Drugs Targeting Protein–Protein Interactions (2006)

Most biological processes involve permanent and nonpermanent interactions between different proteins, and many protein complexes play a key role in various human diseases. Therefore, molecules that prevent the formation of these protein complexes could be valuable new therapeutic agents to treat these diseases. Protein interfaces have not evolved to bind low-molecular-weight molecules, as is the case with enzyme catalytic sites. It is therefore difficult to identify small compounds that inhibit protein-protein interactions. However, there is considerable diversity in the structure of protein interfaces, some of which may be more attractive than others for medicinal chemistry. One of the main challenges in drug discovery is to identify these interfaces and to exploit their properties to make marketable drugs. Herein, the properties of protein interfaces are discussed in light of their use as drug targets.
Modulation of cell surface heparan sulfate structure by growth of cells in the presence of chlorate (1989)

Swiss mouse 3T3 cells, when grown in the presence of 5 mM chlorate, an inhibitor of PAPS synthesis, produce heparan sulfate glycosaminoglycan chains containing only about 8% of the sulfate normally present and which have lost the ability to bind to fibronectin. These undersulfated chains are sensitive to nitrous acid at pH 4.5, indicating that many glucosaminyl residues have unsubstituted amino groups. The iduronic acid content of the heparan sulfate produced in the presence of chlorate is reduced to less than 7% as compared to the 36% in that from untreated cells. The chlorate-treated cells do not demonstrate any alterations in their growth control. However, the spreading behavior of these cells is altered to a flat rounded morphology compared to the more typical fibroblastic appearance of the untreated cell. The sulfation of chondroitin chains is also inhibited, but at a lower chlorate concentration which does not alter growth control or the spreading ability of the cells. These data indicate that (a) 3T3 cell surface heparan sulfate proteoglycan is not involved in growth control but may be involved in cell spreading, (b) the use of chlorate should be a valuable method for the study of the biosynthesis and structure/function relationships of sulfated glycosaminoglycans, and (c) the temporal sequence of the heparan sulfate chain modification reactions predicted from results of studies with cell-free extracts also operates in the cell.
Isolation-only transactions for mobile computing (1994)

article Free Access Share on Isolation-only transactions for mobile computing Authors: Qi Lu School of Computer Science, Carnegie Mellon University School of Computer Science, Carnegie Mellon UniversityView Profile , M. Satyanaranyanan School of Computer Science, Carnegie Mellon University School of Computer Science, Carnegie Mellon UniversityView Profile Authors Info & Claims ACM SIGOPS Operating Systems ReviewVolume 28Issue 2April 1994pp 81–87https://doi.org/10.1145/198153.198164Published:01 April 1994Publication History 40citation405DownloadsMetricsTotal Citations40Total Downloads405Last 12 Months31Last 6 weeks6 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my AlertsNew Citation Alert!Please log in to your account Publisher SiteeReaderPDF
Thermodynamics and stoicheiometry of the binding of substrate analogues to uricase (1980)

The subunit composition, metal content, substrate-analogue binding and thermal stability of Aspergillus flavus uricase were determined. A. flavus uricase is a tetramer and contains no copper, iron or any other common prosthetic group. Analytical-gel-filtration and equilibrium-dialysis experiments showed one binding site per subunit for urate analogues. The free energy of xanthine binding was -30.5 kJ (-7.3 kcal)/mol of subunit by equilibrium dialysis and -30.1 kJ (-7.2 kcal)/mol of subunit by microcalorimetry. The enthalpy change for xanthine binding was -15.9 kJ (-3.8 kcal)/mol of subunit when determined from the temperature-dependence of the equilibrium constant and -18.0 kJ (-4.3 kcal)/mol of subunit when measured microcalorimetrically. The thermal inactivation rate of A. flavus uricase increases as protein concentration is decreased. This concentration-dependent instability is not due to subunit dissociation.
Modulation of HLA class I expression in multidrug-resistant human rhabdomyosarcoma cells. (2003)

An abnormal HLA expression has been detected in some tumors including rhabdomyosarcoma (RMS). Classical cytotoxic treatment of these tumors, the most common childhood soft tissue malignancy, may induce multidrug resistance (MDR) associated with the expression of a 170-kDa membrane-associated glycoprotein (P-glycoprotein). In order to analyse the connection between modulation of HLA expression and the development of the MDR phenotype mediated by P-glycoprotein in RMS, we used three resistant RMS cell lines; two of these resistant cell lines (TE.32.7.DAC and RD-DAC) were established by in vitro exposure to actinomycin D, a drug of choice in the treatment of RMS; the resistant RMS- GR cell line was established from an embryonal RMS tumor after polychemotherapy. Our results showed that all the resistant cell lines showed a significant increase in the expression of HLA class I surface antigens in comparison to drug-sensitive cells. Blockade of P-glycoprotein with verapamil led to a decrease in HLA class I expression in RMS resistant cell lines. However, no modulation of HLA class II expression was observed in any of the three analyzed cell lines. These findings support the hypothesis that the development of resistance mediated by mdr 1/P-glycoprotein, directly influences the expression of HLA class I in RMS cells, inducing to upregulation. This effect may be relevant to the application in RMS of immunotherapy against tumor-associated antigens presented by HLA class I molecules.
EGFR Mutations and Resistance to Irreversible Pyrimidine-Based EGFR Inhibitors (2015)

Our findings provide insights into resistance mechanisms to irreversible pyrimidine-based EGFR inhibitors and identify specific genomic contexts in which sensitivity is retained to existing clinical EGFR inhibitors. These findings will guide the development of new strategies to inhibit EGFR.
Binding to Protein Targets of Peptidic Leads Discovered by Phage Display: Crystal Structures of Streptavidin-Bound Linear and Cyclic Peptide Ligands Containing the HPQ Sequence (1995)

The streptavidin-bound crystal structures of two disulfide-bridge cyclic peptides (cyclo-Ac-[CHPQGPPC]-NH2 and cyclo-Ac-[CHPQFC]-NH2) and of a linear peptide (FSHPQNT) were determined, as well as the structure of apostreptavidin (streptavidin-sulfate). Both the linear and disulfide-bridged cyclic peptides studied share a common HPQ conformation and make common interactions with streptavidin, although significant differences in structures and interactions occur for flanking residues among the complexes. The conformation of the linear peptide in the crystal structure of streptavidin-FSHPQNT was found to differ from that in the same complex published [Weber, P. C., Pantoliano, M. W., & Thompson, L. D. (1992) Biochemistry 31, 9350-9354]. In the present investigation, the HPQNT portion of the ligand is well-defined with some density defining the Phe, whereas in the investigation of Weber et al. only the HPQ segment of the bound peptide could be interpreted. Both bound cyclic peptides adopt a beta-turn involving an H-bond between the His main chain carbonyl and the main chain amide NH of the i+3 residue. In the streptavidin-bound cyclo-Ac-[CHPQFC]-NH2 structure, there is an additional H-bond, indicative of alpha-helix, between the main chain His carbonyl and the main chain C-terminal Cys amide NH group. Binding interactions for both cyclic and linear peptides include direct H-bonds, H-bonds mediated by tightly bound water molecules, and hydrophobic interactions. The above structures and that of streptavidin-biotin in the literature are compared and discussed in the context of structure-based ligand design.
Cholinergic innervation in the human hippocampal formation including the entorhinal cortex (1994)

The cholinergic innervation of the hippocampal formation is thought to play an important role in memory processes, but its organization in humans has not been described in detail. We studied the cholinergic innervation of the human hippocampal formation by means of immunohistochemistry with polyclonal antisera directed against acetylcholinesterase (AChE), choline acetyltransferase (ChAT), and the low-affinity (p75) nerve growth factor receptor (NGFR). The density of ChAT-like immunoreactive (ChAT-li) fibers differed substantially among the various regions, in general paralleling the pattern of AChE-li staining. One notable exception was the presence of AChE-li cell bodies. In contrast, ChAT immunoreactivity was associated only with fibers and terminals. NGFR-li staining corresponded closely to the ChAT-li fiber pattern. ChAT-li fibers in the CA fields diffusely filled the stratum pyramidale and extended into the stratum oriens and radiatum as well. The highest density was consistently observed in CA4 and CA3 subfields. Staining decreased from CA4 to CA1 and was substantially less dense in the subicular complex. In the entorhinal cortex, the ChAT- and NGFR-li fiber innervation displayed a laminar pattern, most intense over the nests of cells in layer II. There was a trend towards an age-related reduction in the density of ChAT- and AChE-li fibers and terminals. Nonetheless, we also found a surprisingly conserved NGFR-li innervation and the presence of occasional NGFR-li pyramidal cells, providing evidence of a plastic response in the brains of the elderly patients.
The effect of “cap” analogs on reovirus mRNA binding to wheat germ ribosomes. Evidence for enhancement of ribosomal binding via a preferred cap conformation. (1978)

A variety of compounds related to the 5'-terminal "cap" (m7GpppN) of eukaryotic mRNA's were chemically synthesized and tested as inhibitors of reovirus mRNA binding to wheat germ ribosomes. Under our conditions of mRNA binding to ribosomes, 7-methyl-, 7-ethyl-, and 7-benzyl-GDP, but not GDP, decreased stable initiation complex formation by 70 to 80% at a concentration of 0.1 mM indicating that 7-substitution, but not a specific substituent, was required for the effect. Elimination of the positive charge on the imidazole of the 7-substituted compounds by treatment with alkali destroyed their inhibitory activity. Similarly, reduction to 8-hydro-m7GDP reversibly decreased the activity of m7GDP. The results were consistent with the hypothesis that the positive charge resulting from 7-alkylation provides an active cap conformer for binding via interaction of phosphate oxygens with the positively charged imidazole moiety. In accord with this suggestion, 7-carboxymethyl GDP and 7,8-dimethyl GDP were found to be less inhibitory than m7GDP. A 2-amino group was also important since m7IDP was less effective than m7GDP and 0.1 mM m7XDP did not inhibit ribosome binding. Other poor inhibitors were 6-Cl-m7GDP and 1,7-dimethyl GDP but N2,7-dimethyl GDP, 2'-deoxy-m7GDP, and m7GppI had essentially the same activity as m7GDP.
Syntheses of Homochiral Multinuclear Ru Complexes Based on Oligomeric Bibenzimidazoles (2007)

The homochiral multinuclear Ru complexes of the oligomeric bibenzimidazoles were synthesized using Lambda-[Ru(bpy)2(py)2][(-)-O,O'-dibenzoyl-l-tartrate].12H2O as an enantiomerically pure building block. The complexations proceed with the retention of configuration to provide well-defined mononuclear, dinuclear, tetranuclear, and octanuclear Ru complexes successfully. The optical purity and the absolute configurations of the complexes were determined by NMR and circular dichroism spectrometry. The rare X-ray structure of a tetranuclear complex Lambda4-[(Ru(bpy)2)4(bis(BiBzIm))](PF6)4 was resolved. The crystallographic analysis reveals that all the four Ru centers have Lambda octahedral configurations, with a Ru-Ru separation of 5.509 A across the bridging bibenzimidazole ligand, which maintains near coplanarity. The UV-vis spectroscopic and electrochemical properties of the homochiral multinuclear assemblies were studied, indicating weak electronic communications between the metal centers.
Short-term high fat-feeding results in morphological and metabolic adaptations in the skeletal muscle of C57BL/6J mice (2007)

The prevalence of the metabolic syndrome (MS) is rapidly increasing all over the world. Consequently, there is an urgent need for more effective intervention strategies. Both animal and human studies indicate that lipid oversupply to skeletal muscle can result in insulin resistance, which is one of the characteristics of the MS. C57BL/6J mice were fed a low-fat (10 kcal%) palm oil diet or a high-fat (45 kcal%; HF) palm oil diet for 3 or 28 days. By combining transcriptomics with protein and lipid analyses we aimed to better understand the molecular events underlying the early onset of the MS. Short-term HF feeding led to altered expression levels of genes involved in a variety of biological processes including morphogenesis, energy metabolism, lipogenesis, and immune function. Protein analysis showed increased levels of the myosin heavy chain, slow fiber type protein, and the complexes I, II, III, IV, and V of the oxidative phosphorylation. Furthermore, we observed that the main mitochondrial membrane phospholipids, phosphatidylcholine and phosphatidylethanolamine, contained more saturated fatty acids. Altogether, these results point to a morphological as well as a metabolic adaptation by promoting a more oxidative fiber type. We hypothesize that after this early positive adaptation, a continued transcriptional downregulation of genes involved in oxidative phosphorylation will result in decreased oxidative capacity at a later stage. Together with increased saturation of phospholipids of the mitochondrial membrane this can result in decreased mitochondrial function, which is a hallmark observed in insulin resistance and Type 2 diabetes.
Preclinical in vivo activity of 2',2'-difluorodeoxycytidine (Gemcitabine) against human head and neck cancer. (1991)

2',2'-Difluorodeoxycytidine (dFdCyd, Gemcitabine) is a new deoxycytidine analogue with striking preclinical antitumor activity in solid tumors from murine and human origin. In this study, dFdCyd was tested for its antitumor effect in human tumor xenografts derived from squamous cell carcinoma of the head and neck (SCCHN). NMRI nude mice bearing s.c. growing tumors with a volume of 50 to 150 mm3 were given i.p. injections of a maximum tolerated dose of 120 mg/kg dFdCyd, every 3 days for four injections. A significant antitumor effect was observed in all five tested SCCHN tumor lines; in four of these lines the median tumor volume doubling time increased more than a 3-fold upon dFdCyd treatment. In two lines dFdCyd was curative (no tumor regrowth 90 days after treatment) in one of six and two of eight xenografts, respectively. Schedule dependency was investigated in three SCCHN lines, showing, in the two most sensitive lines, that treatment with a 3-day interval was superior to the schedules with daily or weekly injections. At equitoxic doses, dFdCyd was more active in this model than the drugs that are clinically used in SCCHN, i.e., cisplatin, methotrexate, 5-fluorouracil, and cyclophosphamide. dFdCyd is a good candidate for clinical trials with SCCHN patients.