gebhart/patrepeval huggingface dataset:
Desmoplastic Small Round Cell Tumor (1998)

In order to investigate the histogenesis and facilitate the diagnosis of desmoplastic small round cell tumor (DSRCT), 39 cases were studied by immunohistochemical methods using a large battery of antibodies directed against a wide variety of epithelial, mesenchymal, and neural-associated proteins. Sixteen of these tumors were also studied by electron microscopy. Thirty-seven of 39 cases reacted for cytokeratin using a "cocktail" of 3 monoclonal antibodies (CAM 5.2/AE1/AE3), 39/39 for desmin, 24/25 for epithelial membrane antigen, 22/27 for vimentin, 18/25 for neuron-specific enolase, 10/15 for CD57 (Leu-7), 3/19 for synaptophysin, 1/22 for chromogranin, 3/19 for muscle-specific actin, 3/16 for alpha-smooth-muscle actin, 11/16 for CD15 (Leu-M1), 5/12 for CA-125, 6/17 for CD99, 9/10 for MOC-31, 2/6 for NB84, 5/7 for Ber-EP4, and 8/9 for the Wilms tumor (WT1) protein. No staining was obtained in any of the cases tested for cytokeratin 5/6 or 20, neurofilament proteins, glial fibrillary acidic protein, peripherin, CA19-9, thrombomodulin, alphafetoprotein, carcinoembryonic antigen, TAG-72 (B72.3), placental alkaline phosphatase, S-100 protein, HMB-45, myoglobin, or for the two myogenic regulatory proteins myogenin and MyoD1. A frequent ultrastructural finding was the presence of juxtanuclear aggregates of intermediate filaments, but microfilaments with densities or Z-band-like material suggestive of either smooth or skeletal muscle differentiation were not seen in any case. Dendritic-like processes containing microtubules and dense core granules were seen in four tumors and all of these tumors reacted for at least one of the neural markers investigated. Although ultrastructural and immunohistochemical studies confirmed previous observations that DSRCTs present epithelial, mesenchymal, and neural phenotypes, a great variation was found in the frequency of expression of the different markers used to demonstrate each line of cell differentiation. The absence of expression of cytokeratin 5/6 and thrombomodulin together with positive staining for CD15, MOC-31, and Ber-EP4 argues against the possible mesothelial origin that has been suggested for this tumor. Additionally since none of the tumors reacted for myogenin or MyoD1, desmin expression in DSRCT cannot be regarded as evidence of skeletal muscle differentiation. Although the histogenesis of DSRCT remains unknown, it is believed that this tumor originates from a progenitor cell with potential for multiphenotypic differentiation.
Effects of a Saccharomyces cerevisiae Culture on Ruminal Bacteria that Utilize Lactate and Digest Cellulose (1997)

The objective of this study was to determine the effects of a yeast (Saccharomyces cerevisiae) culture on lactate utilization and cellulose digestion by ruminal bacteria. Growth of Selenomonas ruminantium HD4 in medium that contained 5 g/L of DL-lactate, Trypticase, and yeast extract was stimulated 7 and 15% by 1 and 5% (vol/vol) yeast culture filtrate respectively. The 1 and 5% yeast culture filtrate stimulated growth of Selenomonas ruminantium H18 and Megasphaera elsdenii B159 and T81 on 5 g/L of DL-lactate in medium without Trypticase or yeast extract. Growth of Fibrobacter succinogenes S85 and Ruminococcus albus B199 on 6 g/L of cellobiose was stimulated by the addition of yeast culture filtrate to medium without Trypticase or yeast extract. The yeast culture filtrate increased the concentrations of acetate and total volatile fatty acids that were produced by Sel. ruminantium HD4 and increased the concentrations of propionate and total volatile fatty acids that were produced by Sel. ruminantium H18 but did not alter end-product formation of M. elsdenii or cellulolytic bacteria. Treatment with yeast culture increased the initial rate but not the extent of cellulose digestion by F. succinogenes S85 and Ruminococcus flavefaciens FD1. Collectively, these results suggest that yeast culture provides soluble growth factors (i.e., organic acids, B vitamins, and amino acids) that stimulate growth of ruminal bacteria that utilize lactate and digest cellulose.
Thrombopoietin (1998)

Although the cellular physiology of megakaryocyte and platelet production has been understood for nearly a decade, the humoral basis of this process has remained enigmatic until recently. “Thrombopoietin — At Last” heralded one editorial1 when the cloning of the chief regulator of megakaryocyte and platelet production was reported.24 The availability of the purified hormone has made possible new insights into many aspects of blood-cell development and provided a way to increase platelet production in patients with bone marrow failure. This review focuses on the physiology of thrombopoietin and megakaryocyte production, with a view to understanding how this information can . . .
AIB1, a Steroid Receptor Coactivator Amplified in Breast and Ovarian Cancer (1997)

Members of the recently recognized SRC-1 family of transcriptional coactivators interact with steroid hormone receptors to enhance ligand-dependent transcription. AIB1, a member of the SRC-1 family, was cloned during a search on the long arm of chromosome 20 for genes whose expression and copy number were elevated in human breast cancers. AIB1 amplification and overexpression were observed in four of five estrogen receptor-positive breast and ovarian cancer cell lines. Subsequent evaluation of 105 unselected specimens of primary breast cancer found AIB1 amplification in approximately 10 percent and high expression in 64 percent of the primary tumors analyzed. AIB1 protein interacted with estrogen receptors in a ligand-dependent fashion, and transfection of AIB1 resulted in enhancement of estrogen-dependent transcription. These observations identify AIB1 as a nuclear receptor coactivator whose altered expression may contribute to development of steroid-dependent cancers.
Combinations of PARP Inhibitors with Temozolomide Drive PARP1 Trapping and Apoptosis in Ewing’s Sarcoma (2015)

Ewing's sarcoma is a malignant pediatric bone tumor with a poor prognosis for patients with metastatic or recurrent disease. Ewing's sarcoma cells are acutely hypersensitive to poly (ADP-ribose) polymerase (PARP) inhibition and this is being evaluated in clinical trials, although the mechanism of hypersensitivity has not been directly addressed. PARP inhibitors have efficacy in tumors with BRCA1/2 mutations, which confer deficiency in DNA double-strand break (DSB) repair by homologous recombination (HR). This drives dependence on PARP1/2 due to their function in DNA single-strand break (SSB) repair. PARP inhibitors are also cytotoxic through inhibiting PARP1/2 auto-PARylation, blocking PARP1/2 release from substrate DNA. Here, we show that PARP inhibitor sensitivity in Ewing's sarcoma cells is not through an apparent defect in DNA repair by HR, but through hypersensitivity to trapped PARP1-DNA complexes. This drives accumulation of DNA damage during replication, ultimately leading to apoptosis. We also show that the activity of PARP inhibitors is potentiated by temozolomide in Ewing's sarcoma cells and is associated with enhanced trapping of PARP1-DNA complexes. Furthermore, through mining of large-scale drug sensitivity datasets, we identify a subset of glioma, neuroblastoma and melanoma cell lines as hypersensitive to the combination of temozolomide and PARP inhibition, potentially identifying new avenues for therapeutic intervention. These data provide insights into the anti-cancer activity of PARP inhibitors with implications for the design of treatment for Ewing's sarcoma patients with PARP inhibitors.
Inhibitory Effect of Ursolic Acid Purified from Origanum majorana L. on the Acetylcholinesterase (2001)

We screened 139 herbal spices in search of the acetylcholinesterase (AChE) inhibitor from natural resources. AChE inhibitors, which enhance cholinergic transmission by reducing the enzymatic degradation of acetylcholine, are the only source of compound currently approved for the treatment of Alzheimer's Disease (AD). Among these herbs, edible plants and spices, the ethanol extract from Origanum majorana L. showed the highest inhibitory effect on AChE in vitro. By sequential fractionation of Origanum majorana L. the active component was finally identified as ursolic acid (3 beta-Hydroxyurs-12-en-28-oic acid). The ursolic acid of Origanum majorana L. inhibited AChE activity in a dose-dependent and competitive/non-competitive type. The Ki value (representing the affinity of the enzyme and inhibitor) of Origanum majorana L. ursolic acid was 6 pM, and that of tacrine was 0.4 nM. The concentration required for 50% enzyme inhibition of the active component (IC50 value) was 7.5 nM, and that of tacrine was 1 nM. This study demonstrated that the ursolic acid of Origanum majorana L. appeared to be a potent AChE inhibitor in Alzheimer's Disease.
USP7 counteracts SCFβTrCP- but not APCCdh1-mediated proteolysis of Claspin (2009)

Claspin is an adaptor protein that facilitates the ataxia telangiectasia and Rad3-related (ATR)-mediated phosphorylation and activation of Chk1, a key effector kinase in the DNA damage response. Efficient termination of Chk1 signaling in mitosis and during checkpoint recovery requires SCF(betaTrCP)-dependent destruction of Claspin. Here, we identify the deubiquitylating enzyme ubiquitin-specific protease 7 (USP7) as a novel regulator of Claspin stability. Claspin and USP7 interact in vivo, and USP7 is required to maintain steady-state levels of Claspin. Furthermore, USP7-mediated deubiquitylation markedly prolongs the half-life of Claspin, which in turn increases the magnitude and duration of Chk1 phosphorylation in response to genotoxic stress. Finally, we find that in addition to the M phase-specific, SCF(betaTrCP)-mediated degradation, Claspin is destabilized by the anaphase-promoting complex (APC) and thus remains unstable in G1. Importantly, we demonstrate that USP7 specifically opposes the SCF(betaTrCP)- but not APC(Cdh1)-mediated degradation of Claspin. Thus, Claspin turnover is controlled by multiple ubiquitylation and deubiquitylation activities, which together provide a flexible means to regulate the ATR-Chk1 pathway.
Heterodimerization of c-erbB2 with different epidermal growth factor receptor mutants elicits stimulatory or inhibitory responses. (1992)

Ligand-induced dimerization of growth factor receptors is crucial for stimulation of their intrinsic protein tyrosine kinase activity promoting receptor autophosphorylation by an intermolecular mechanism. Moreover, the suppressive and negative dominant action of defective epidermal growth factor receptor (EGFR) was shown to be caused by formation of inactive heterodimers with normal EGFR leading to diminished biological signaling. In this report we explore the structural requirements and functional significance of heterodimerization between EGFR and HER2. HER2 (also called c-erbB-2 or neu) is a member of the EGFR family whose natural ligand is still unknown. We show that in response to EGF, wild type EGFR and various EGFR mutants were able to undergo heterodimerization with HER2. Addition of EGF to transfected cells co-expressing HER2 with a kinase negative point mutant of EGFR (K721A) stimulated heterodimer formation, tyrosine phosphorylation of K721A and HER2, and tyrosine phosphorylation of one of their known substrates, phospholipase C gamma. However, the binding of EGF to transfected cells co-expressing HER2 together with another EGFR mutant CD533 (a deletion mutant lacking most of the cytoplasmic domain of EGFR) caused heterodimerization and inhibition of tyrosine kinase activity. It appears therefore that EGF-induced heterodimerization of EGFR and HER2 can promote either stimulatory or inhibitory influences on kinase activity. We propose that the nature of receptor interactions on the cell surface can either activate or inhibit the initiation of growth factor-controlled cellular signaling.
Assessment of fluid balance by measurement of skin tissue thickness during clinical anaesthesia (2002)

Non-invasive determinations of skin tissue thickness by the presented ultrasonic device appears to give additional information on fluid intake and distribution during clinical anaesthesia.
Expression of epidermal growth factor receptor in human glioblastoma multiforme (1993)

The expression of epidermal growth factor receptor was determined in a series of 88 patients with glioblastoma multiforme using a monoclonal antibody to the receptor. Positive staining was seen in 17 patients but this did not have prognostic significance when compared with known clinical prognostic factors using a computer model. The significance of receptor expression in these tumours is discussed.
Roux-en-Y biliary diversion: a worthwhile procedure? (1996)

The Roux-en-Y biliary diversion has varied in popularity, with poor results recently reported. A retrospective case note review was undertaken of all patients who underwent Roux-en-Y diversion, in a single consultant practice to assess a single clinician's results. Thirty-seven consecutive patients who underwent biliary diversion were studied: 22 had gastric malignancy and 15 had benign biliary reflux. The benign group revealed improvement in 80% with 40% being entirely asymptomatic and 66% being medication free. In the malignant disease group 15 patients were Visick grade I or II post-operatively; two were classified as Visick IV but one was converted to grade I after further gastric resection. The 30-day mortality in this group was 14 and 50% at 5 years. Good or satisfactory results can be obtained from Roux-en-Y biliary diversion for patients with benign (80% satisfied) and malignant (84% satisfied) disorders but care with patient selection in the benign group is required.
Influenza A-specific, HLA-A2.1-restricted cytotoxic T lymphocytes from HLA-A2.1 transgenic mice recognize fragments of the M1 protein (1991)

Previous studies have indicated that in transgenic mice expressing human class I MHC molecules, it is difficult to demonstrate a significant CTL response to a viral Ag in the context of the transgenic molecule. In this paper, a procedure is reported for the isolation of influenza-specific murine CTL restricted by the human class I molecule HLA-A2.1. The principal specificity of such CTL is for a fragment of the influenza M1 protein that has been previously shown to be immunodominant for human HLA-A2.1-restricted CTL. CTL of this specificity were also established through the use of peptide-pulsed rather than virus-infected stimulators. The dependence of murine CTL recognition upon peptide length and HLA-A2 structure was established to be similar to that previously reported for human CTL. However, the fine specificity of CTL maintained on virus-infected stimulators was somewhat different from that of CTL maintained with M1 peptide. This suggests that differences in surface density or peptide structure between peptide-pulsed and virus-infected stimulators may result in the outgrowth of T cells with different receptor structures. The immunodominance of the M1 peptide determinant in both mice and humans suggests that species-specific differences in TCR structure, Ag-processing systems, and self-tolerance are of less importance than limitations on the ability of antigenic peptides to bind to appropriate class I molecules. These results thus establish the utility of the transgenic system for the identification of human class I MHC-restricted T cell epitopes.
Location based applications for mobile augmented reality (2003)

In this work we investigate building indoor location based applications for a mobile augmented reality system. We believe that augmented reality is a natural interface to visualize spacial information such as position or direction of locations and objects for location based applications that process and present information based on the user&amp;apos;s position in the real world. To enable such applications we construct an indoor tracking system that covers a substantial part of a building. It is based on visual tracking of fiducial markers enhanced with an inertial sensor for fast rotational updates. To scale such a system to a whole building we introduce a space partitioning scheme to reuse fiducial markers throughout the environment. Finally we demonstrate two location based applications built upon this facility, an indoor navigation aid and a library search application.
Mapping Targetable Sites on Human Telomerase RNA Pseudoknot/Template Domain Using 2′-OMe RNA-interacting Polynucleotide (RIPtide) Microarrays (2012)

Most cellular RNAs engage in intrastrand base-pairing that gives rise to complex three-dimensional folds. This self-pairing presents an impediment toward binding of the RNA by nucleic acid-based ligands. An important step in the discovery of RNA-targeting ligands is therefore to identify those regions in a folded RNA that are accessible toward the nucleic acid-based ligand. Because the folding of RNA targets can involve interactions between nonadjacent regions and employ both Watson-Crick and non-Watson-Crick base-pairing, screening of candidate binder ensembles is typically necessary. Microarray-based screening approaches have shown great promise in this regard and have suggested that achieving complete sequence coverage would be a valuable attribute of a next generation system. Here, we report a custom microarray displaying a library of RNA-interacting polynucleotides comprising all possible 2'-OMe RNA sequences from 4- to 8-nucleotides in length. We demonstrate the utility of this array in identifying RNA-interacting polynucleotides that bind tightly and specifically to the highly conserved, functionally essential template/pseudoknot domain of human telomerase RNA and that inhibit telomerase function in vitro.
Energy Band-Gap Engineering of Graphene Nanoribbons (2007)

We investigate electronic transport in lithographically patterned graphene ribbon structures where the lateral confinement of charge carriers creates an energy gap near the charge neutrality point. Individual graphene layers are contacted with metal electrodes and patterned into ribbons of varying widths and different crystallographic orientations. The temperature dependent conductance measurements show larger energy gaps opening for narrower ribbons. The sizes of these energy gaps are investigated by measuring the conductance in the nonlinear response regime at low temperatures. We find that the energy gap scales inversely with the ribbon width, thus demonstrating the ability to engineer the band gap of graphene nanostructures by lithographic processes.
In vitro initiation of DNA replication in simian virus 40 chromosomes. (1987)

A soluble system has been developed that can initiate DNA replication de novo in simian virus 40 (SV40) chromatin isolated from virus-infected monkey cells as well as in circular plasmid DNA containing a functional SV40 origin of replication (ori). Initiation of DNA replication in SV40 chromatin required the soluble fraction from a high-salt nuclear extract of SV40-infected cells, a low-salt cytosol fraction, polyethylene glycol, and a buffered salts solution containing all four standard deoxyribonucleoside triphosphates. Purified SV40 large tumor antigen (T-ag) partially substituted for the high-salt nucleosol, and monoclonal antibodies directed against SV40 T-ag inhibited DNA replication. Replication began at ori and proceeded bidirectionally to generate replicating DNA intermediates in which the parental strands remained covalently closed, as observed in vivo. Partial inhibition of DNA synthesis by aphidicolin resulted in accumulation of newly initiated replicating intermediates in this system, a phenomenon not observed under conditions that supported completion of replication only. However, conditions that were optimal for initiation of replication repressed conversion of late-replicating intermediates into circular DNA monomers. Most surprising was the observation that p-n-butylphenyl-dGTP, a potent and specific inhibitor of DNA polymerase-alpha, failed to inhibit replication of SV40 chromatin under conditions that completely inhibited replication of plasmid DNA containing the SV40 ori and either purified or endogenous DNA polymerase-alpha activity. In contrast, all of these DNA synthesis activities were inhibited equally by aphidicolin. Therefore, DNA replication in mammalian cells is carried out either by DNA polymerase-alpha that bears a unique association with chromatin or by a different enzyme such as DNA polymerase-delta.
Parameters Affecting Ethyl Ester Production bySaccharomyces cerevisiaeduring Fermentation (2007)

ABSTRACT Volatile esters are responsible for the fruity character of fermented beverages and thus constitute a vital group of aromatic compounds in beer and wine. Many fermentation parameters are known to affect volatile ester production. In order to obtain insight into the production of ethyl esters during fermentation, we investigated the influence of several fermentation variables. A higher level of unsaturated fatty acids in the fermentation medium resulted in a general decrease in ethyl ester production. On the other hand, a higher fermentation temperature resulted in greater ethyl octanoate and decanoate production, while a higher carbon or nitrogen content of the fermentation medium resulted in only moderate changes in ethyl ester production. Analysis of the expression of the ethyl ester biosynthesis genes EEB1 and EHT1 after addition of medium-chain fatty acid precursors suggested that the expression level is not the limiting factor for ethyl ester production, as opposed to acetate ester production. Together with the previous demonstration that provision of medium-chain fatty acids, which are the substrates for ethyl ester formation, to the fermentation medium causes a strong increase in the formation of the corresponding ethyl esters, this result further supports the hypothesis that precursor availability has an important role in ethyl ester production. We concluded that, at least in our fermentation conditions and with our yeast strain, the fatty acid precursor level rather than the activity of the biosynthetic enzymes is the major limiting factor for ethyl ester production. The expression level and activity of the fatty acid biosynthetic enzymes therefore appear to be prime targets for flavor modification by alteration of process parameters or through strain selection.
Synthesis, Properties and Applications of Papillomavirus-Like Particles (1996)

Papillomavirus-like particles can be obtained by expression of the major capsid protein L1 alone or by coexpression with the minor capsid protein L2 in various systems. Virus-like particles (VPLs) and virions have very similar capsid structures. Immunization with VLPs yields antibodies neutralizing virions in vitro. Vaccination of animals with VLPs has been shown to protect against viral challenge. VLPs of human papillomavirus (HPV) are therefore the most promising vaccine candidate to prevent infections with HPVs associated with cervical cancer, the most frequent carcinoma in women worldwide.