gebhart/patrepeval huggingface dataset:
Removal of Normal Competition Increases Proliferation of Pre-Leukemic Cells in a Mouse Model of Pre-B Acute Lymphoblastic Leukemia. (2009)

Abstract Abstract 1430 Poster Board I-453 B cell precursor (BCP) acute lymphoblastic leukemia (ALL) is the most common childhood malignancy. While the peak age of onset for this disease is 4 years, abnormal cells that will eventually give rise to disease can be detected in blood taken from patients at birth. Interestingly, similar abnormal cell populations can also be detected in blood taken at birth from many children who do not go onto develop ALL. Understanding the factors that influence the survival and expansion or elimination of these abnormal pre-leukemic cells will shed light on the process of leukemogenesis and may suggest strategies for the prevention of BCP-ALL progression. We have used a mouse model of BCP-ALL to investigate the influence of normal immune cells on the pre-leukemic population. An abnormal BCP population arises in Eμ-RET (RFP) transgenic mice during fetal development, with overt leukemia developing between 3 and 9 months of age. We show that purified BCP from bone marrow of 4-week old pre-leukemic RFP mice undergo rapid expansion when adoptively transferred into immune-deficient mice, in many cases reaching white blood cell counts of &gt;105 (with &gt;90% showing the abnormal BCP phenotype). Secondary and tertiary transfer of expanded BCP into immune-deficient mice again produced a severe BCP lymphoproliferative disease. Such an expansion was not observed when purified BCP were transferred into wild-type mice or when unsorted pre-leukemic RFP bone marrow was transferred into immune-deficient mice. In addition, outgrowth of the abnormal cells was significantly curtailed if the purified RFP cells were mixed with a tenfold excess of wild-type bone marrow cells prior to adoptive transfer. This inhibition of BCP outgrowth was not achieved with Rag1-deficient bone marrow cells, suggesting that competition with normal adaptive immune cells for limited growth factors may impair the expansion of RFP pre-leukemic cells. Consistent with this hypothesis, blockade of the IL-7 receptor on pre-leukemic cells abrogated their expansion following adoptive transfer. As production of IL-7 is elevated in lymphopenic settings, we evaluated the impact of T cell-depletion on pre-leukemic cells in RFP mice. Pre-leukemic cell populations were significantly elevated in the spleen (31.3% +/- 15.4 vs 9% +/- 9, p&lt;0.01) and blood (17% +/-19.2 vs 3% +/- 4.8, p&lt;0.05) of T cell-depleted mice compared to controls. Taken together, these results suggest that competition for growth factors such as IL-7 may be a limiting step in the early expansion of pre-leukemic cell populations and may provide a mechanistic link between immune responses and pediatric ALL through the cytokine-mediated expansion of the pre-leukemic cell pool. Disclosures No relevant conflicts of interest to declare.
Models and Methods to Evaluate Transport of Drug Delivery Systems Across Cellular Barriers (2013)

Sub-micrometer carriers (nanocarriers; NCs) enhance efficacy of drugs by improving solubility, stability, circulation time, targeting, and release. Additionally, traversing cellular barriers in the body is crucial for both oral delivery of therapeutic NCs into the circulation and transport from the blood into tissues, where intervention is needed. NC transport across cellular barriers is achieved by: (i) the paracellular route, via transient disruption of the junctions that interlock adjacent cells, or (ii) the transcellular route, where materials are internalized by endocytosis, transported across the cell body, and secreted at the opposite cell surface (transyctosis). Delivery across cellular barriers can be facilitated by coupling therapeutics or their carriers with targeting agents that bind specifically to cell-surface markers involved in transport. Here, we provide methods to measure the extent and mechanism of NC transport across a model cell barrier, which consists of a monolayer of gastrointestinal (GI) epithelial cells grown on a porous membrane located in a transwell insert. Formation of a permeability barrier is confirmed by measuring transepithelial electrical resistance (TEER), transepithelial transport of a control substance, and immunostaining of tight junctions. As an example, ~200 nm polymer NCs are used, which carry a therapeutic cargo and are coated with an antibody that targets a cell-surface determinant. The antibody or therapeutic cargo is labeled with (125)I for radioisotope tracing and labeled NCs are added to the upper chamber over the cell monolayer for varying periods of time. NCs associated to the cells and/or transported to the underlying chamber can be detected. Measurement of free (125)I allows subtraction of the degraded fraction. The paracellular route is assessed by determining potential changes caused by NC transport to the barrier parameters described above. Transcellular transport is determined by addressing the effect of modulating endocytosis and transcytosis pathways.
α‐enolase: a promising therapeutic and diagnostic tumor target (2011)

α-enolase (ENOA) is a metabolic enzyme involved in the synthesis of pyruvate. It also acts as a plasminogen receptor and thus mediates activation of plasmin and extracellular matrix degradation. In tumor cells, ΕΝΟΑ is upregulated and supports anaerobic proliferation (Warburg effect), it is expressed at the cell surface, where it promotes cancer invasion, and is subjected to a specific array of post-translational modifications, namely acetylation, methylation and phosphorylation. Both ENOA overexpression and its post-translational modifications could be of diagnostic and prognostic value in cancer. This review will discuss recent information on the biochemical, proteomics and immunological characterization of ENOA, particularly its ability to trigger a specific humoral and cellular immune response. In our opinion, this information can pave the way for effective new therapeutic and diagnostic strategies to counteract the growth of the most aggressive human disease.
Thermodynamic analysis and optimization of RWGS processes for solar syngas production from CO2 (2016)

Process systems were investigated for syngas production from CO 2 and renewable energy (solar) by the reverse water‐gas shift (RWGS) and the reverse water‐gas shift chemical looping (RWGS‐CL) process. Thermodynamic analysis and optimization was performed to maximize the solar‐to‐syngas (StS) efficiency η StS . Special emphasis was laid on product gas separation. For RWGS‐CL, maximum StS efficiencies of 14.2 and 14.4% were achieved without and with heat integration, respectively. The StS efficiency is dictated by the low overall efficiency of H 2 production. RWGS‐CL is most beneficial for the production of pure CO, where the StS efficiency is one percent point higher compared to that of the RWGS process with heat integration. Heat integration leads to significant reductions in external heat demand since most of the gas phase process heat can be integrated. The StS efficiencies for RWGS and RWGS‐CL achieve the same level as the reported values for solar thermochemical syngas production. © 2016 American Institute of Chemical Engineers AIChE J , 63: 15–22, 2017
I n s i t u preparation of Y-Ba-Cu-O superconducting thin films by magnetron sputtering (1988)

Thin superconducting films of YBa2 Cu3 O7 have been prepared by magnetron sputtering from targets of sintered material in an oxygen-argon atmosphere. The compositional and structural properties were studied by Rutherford backscattering and x-ray diffraction. The films were deposited at substrate temperatures between 580 and 800 °C. It was found that the material grows in the oxygen deficient tetragonal phase. In situ heat treatment at 430 °C in pure O2 atmosphere generates the orthorhombic structure and the films on sapphire and SrTiO3 coated sapphire substrates show the full superconducting transition at 83 K.
Identification of DPPA4 and DPPA2 as a novel family of pluripotency-related oncogenes (2013)

In order to identify novel pluripotency-related oncogenes, an expression screen for oncogenic foci-inducing genes within a retroviral human embryonic stem cell cDNA library was conducted. From this screen, we identified not only known oncogenes but also intriguingly the key pluripotency factor, DPPA4 (developmental pluripotency-associated four) that encodes a DNA binding SAP domain-containing protein. DPPA4 has not been previously identified as an oncogene but is highly expressed in embryonal carcinomas, pluripotent germ cell tumors, and other cancers. DPPA4 is also mutated in some cancers. In direct transformation assays, we validated that DPPA4 is an oncogene in both mouse 3T3 cells and immortalized human dermal fibroblasts. Overexpression of DPPA4 generates oncogenic foci (sarcoma cells) and causes anchorage-independent growth. The in vitro transformed cells also give rise to tumors in immunodeficient mice. Furthermore, functional analyses indicate that both the DNA-binding SAP domain and the histone-binding C-terminal domain are critical for the oncogenic transformation activity of DPPA4. Downregulation of DPPA4 in E14 mouse embryonic stem cells and P19 mouse embryonic carcinoma cells causes decreased cell proliferation in each case. In addition, DPPA4 overexpression induces cell proliferation through genes related to regulation of G1/S transition. Interestingly, we observed similar findings for family member DPPA2. Thus, we have identified a new family of pluripotency-related oncogenes consisting of DPPA2 and DPPA4. Our findings have important implications for stem cell biology and tumorigenesis.
Growth phase-regulated expression of bolA and morphology of stationary-phase Escherichia coli cells are controlled by the novel sigma factor sigma S (1991)

The novel sigma factor (sigma S) encoded by rpoS (katF) is required for induction of many growth phase-regulated genes and expression of a variety of stationary-phase phenotypes in Escherichia coli. Here we demonstrate that wild-type cells exhibit spherical morphology in stationary phase, whereas rpoS mutant cells remain rod shaped and are generally larger. Size reduction of E. coli cells along the growth curve is a continuous and at least biphasic process, the second phase of which is absent in rpoS-deficient cells and correlates with induction of the morphogene bolA in wild-type cells. Stationary-phase induction of bolA is dependent on sigma S. The "gearbox" a characteristic sequence motif present in the sigma S-dependent growth phase- and growth rate-regulated bolAp1 promoter, is not recognized by sigma S, since stationary-phase induction of the mcbA promoter, which also contains a gearbox, does not require sigma S, and other sigma S-controlled promoters do not contain gearboxes. However, good homology to the potential -35 and -10 consensus sequences for sigma S regulation is found in the bolAp1 promoter.
A HYBRID CONTINUOUS SPEECH RECOGNITION SYSTEM USING SEGMENTAL NEURAL NETS WITH HIDDEN MARKOV MODELS (1993)

Up till recently, state-of-the-art, large vocabulary, continuous speech recognition (CSR) had employed hidden Markov modeling (HMM) to model speech sounds. In an attempt to improve over HMM we developed a hybrid system that integrates HMM technology with neural networks. We present the concept of a Segmental Neural Net (SNN) for phonetic modeling in CSR. By taking into account all the frames of a phonetic segment simultaneously, the SNN overcomes the well-known conditional-independence limitation of HMMs. We have developed a novel hybrid SNN/HMM system that combines the advantages of SNNs and HMMs using a multiple hypothesis (or N-best) paradigm. In this system, we generate likely phonetic segmentations from the HMM N-best list of word sequences, which are scored by the SNN. The HMM and SNN scores are then combined to optimize performance. In several speaker-independent, 1000-word CSR tests, the error rate for the hybrid system dropped 20% from that of a state-of-the-art HMM system alone.
Influence of crystal polarity on the properties of Pt/GaN Schottky diodes (2000)

Si-doped epitaxial GaN layers with Ga- and N-face polarity were grown by plasma-induced molecular-beam epitaxy (PIMBE) in order to characterize the influence of polarity on the electrical properties of Pt Schottky diodes. Different barrier heights for Pt onto these two materials are obtained from the dependence of the effective barrier height versus ideality factor, determined by I–V measurements to be 1.1 and 0.9 eV for Ga- and N-face GaN, respectively. C–V measurements confirm the greater barrier heights for Ga-face material. A possible explanation for this behavior can be a different band bending of the conduction and valence band, inferred from the self-consistent solution of the Schrödinger–Poisson equation, including polarization-induced surface and interface charges, which result from the different spontaneous polarization in epitaxial layers with different polarity.
Structure and Function of Ferricyanide in the Formation of Chromate Conversion Coatings on Aluminum Aircraft Alloy (1999)

Raman and infrared spectroscopy were used to determine the structure of and its reaction products in chromate conversion coatings (CCCs) on AA 2024-T3 aluminum aircraft alloy. In addition, Raman spectroscopy was used to monitor CCC growth rates and their dependence on coating bath composition. The IR and Raman spectra of the air‐dried CCC corresponded to those of Berlin green, a polymer, and physisorbed on . No other cyano‐containing products were observed. When was excluded from the coating bath, CCC formation rate greatly decreased. In addition, it was observed that could rapidly oxidize AA 2024-T3, and rapidly reduced Cr(VI) in bath conditions. These results indicate a redox mediation action for , which greatly increases the reduction of Cr(VI) to Cr(III) by the alloy. This process is normally quite slow, and redox mediation by is critical to CCC formation. could substitute for to produce a chromate film with properties very similar to a conventional CCC. The results establish redox mediation as the mechanism of acceleration of CCC formation, but provide no evidence for any additional role of in corrosion protection. © 1999 The Electrochemical Society. All rights reserved.
The role of amino-terminal residues of the heavy chain of factor IXa in the binding of its cofactor, factor VIIIa (1994)

The purpose of this study is to determine which residues of the factor IXa heavy chain are important for interaction with the cofactor of factor IXa, factor VIIIa. Because the monoclonal antibody (MoAb) FXC008 inhibits interaction between factors IXa and VIIIa, and because it also reacts with residues 181–310 of the factor IXa heavy chain, we used the computer-modelled structure of the factor IXa heavy chain to select charged surface residues likely to interact with FXC008 and/or factor VIIIa. We made mutations in the region of residues 181–310 of the heavy chain of factor IX, and replaced these amino acids individually with those located at the same position in factor X. The mutated factor IX retained complete clotting activity and thus interacted normally with factor VIIIa. Five mutant proteins (factor IXK214F, factor IXK228R, factor IXE240Q, factor IXK247V, and factor IXN260K) reacted with heavy chain-specific MoAbs FXC008 and A-5. Neither factor IXD276K nor factor IXR248H bound to FXC008. Factor IXR252V had reduced affinity to FXC008. Our results suggest the following: (1) factor IXa residues 214, 228, 240, 247, 248, 252, 260, and 276 are not involved in specific interaction with factor VIIIa; and (2) the FXC008 and factor VIIIa binding sites may not share critical residues.
Intrinsic procoagulant surface induced by hypercholesterolaemia on rabbit aortic endothelium (1993)

The effect of hyperlipidaemia on endothelial cell haemostatic properties was examined using ex vivo studies on aortic segments obtained from fat-fed Chinchilla rabbits, mounted in a template device which exposed the luminal surface. Exposure of arterial endothelium to lipids resulted in marked enhancement of externally exposed anionic phospholipids, detected using either fluorescence microscopy with the probe merocyanine 540 or by binding of 125I-polymyxin B and 125I-Annexin V. Consistent with the known procoagulant properties of anionic phospholipid, following the lipid and cholesterol-rich diet intake, intact endothelial cells demonstrated enhanced binding of radioiodinated factors IX/IXa and Xa, and enhanced factor IXa/VIII-dependent factor X activation and factor Xa-factor Va-mediated prothrombin activation. Both factor Xa and thrombin formation were blocked, in large part, by polymyxin B, suggesting dependence of the reaction on anionic phospholipids. Consistent with these results, evidence of increased activation of the coagulation mechanism in vivo was observed in hyperlipidaemic animals, as assessed by a three-fold increase in levels of circulating antithrombin-protease complexes, compared with normolipidaemic controls.
Genetically engineered HSV in the treatment of glioma: a review (2000)

Central nervous system malignancies, particularly glioblastoma multiforme, pose significant problems for the development of novel therapeutics. In the absence of advances with standard surgical and chemotherapeutic approaches, the utilisation of genetically engineered viruses, both as direct oncolytic agents as well as for the delivery of foreign proteins, represents a significant advance in the experimental approach to management of patients with these incurable tumours. Among other viruses, HSV offers an opportunity to directly influence the replication of tumour cells within the central nervous system. Because of its propensity to replicate in neuronal tissue as well as its large coding capacity, it provides an experimental model for the development of novel therapeutics. The status of these experimental approaches will be summarised in this review.
Etiology of Human Disease at the DNA Level (1991)

In this collection of review articles based on papers presented at a Nobel Symposium, biomedical researchers highlight advances in mapping of human disease traits, molecular characterization of genetic defects, investigation of multigenic disorders, gene replacement in humans and animals models, and diagnosis and therapy of genetic disease. Experts examine the genetics of colorectal cancer, the role of homeotic and other development-regulating genes in human malformations, the proteins of blood coagulation and their genes, DNA markers in neurogentic disorders, genetic predisposition to diabetes mellitus, and genetic control of plasma fibrinogen levels. Coverage of diagnosis and therapy includes discussions of high-resolution gene mapping by fluorescent in situ hybridization, diagnosis of genetic disease in preimplantation embryos, and marrow transplantation as a model system for corrections of genetic disease.
A Novel Pathogen- and Wound-Inducible Tobacco (Nicotiana tabacum) Protein with Antifungal Activity (1994)

A novel pathogen- and wound-inducible antifungal protein of 20 kD was purified from tobacco (Nicotiana tabacum) Samsun NN leaves inoculated with tobacco mosaic virus (TMV). The protein, designated CBP20, was purified by chitin-affinity chromatography and gel filtration. In vitro assays demonstrated that CBP20 exhibits antifungal activity toward Trichoderma viride and Fusarium solani by causing lysis of the germ tubes and/or growth inhibition. In addition it was shown that CBP20 acts synergistically with a tobacco class I chitinase against F. solani and with a tobacco class I beta-1,3-glucanase against F. solani and Alternaria radicina. Analysis of the protein and corresponding cDNAs revealed that CBP20 contains an N-terminal chitin-binding domain that is present also in the class I chitinases of tobacco, the putative wound-induced (WIN) proteins of potato, WIN1 and WIN2, and several plant lectins. The C-terminal domain of CBP20 showed high identity with tobacco pathogenesis-related (PR) proteins, PR-4a and PR-4b, tomato PR-P2, and potato WIN1 and WIN2. CBP20 is synthesized as a preproprotein, which is processed into the mature protein by the removal of an N-terminal signal peptide and a C-terminal propeptide, most likely involved in the vacuolar targeting of the protein. The intracellular localization of CBP20 and its induction upon TMV infection and wounding indicate that CBP20 is the first class I PR-4 type protein purified.
A tele-operated mobile ultrasound scanner using a light-weight robot (2005)

This paper presents a new tele-operated robotic chain for real-time ultrasound image acquisition and medical diagnosis. This system has been developed in the frame of the Mobile Tele-Echography Using an Ultralight Robot European Project. A light-weight six degrees-of-freedom serial robot, with a remote center of motion, has been specially designed for this application. It holds and moves a real probe on a distant patient according to the expert gesture and permits an image acquisition using a standard ultrasound device. The combination of mechanical structure choice for the robot and dedicated control law, particularly nearby the singular configuration allows a good path following and a robotized gesture accuracy. The choice of compression techniques for image transmission enables a compromise between flow and quality. These combined approaches, for robotics and image processing, enable the medical specialist to better control the remote ultrasound probe holder system and to receive stable and good quality ultrasound images to make a diagnosis via any type of communication link from terrestrial to satellite. Clinical tests have been performed since April 2003. They used both satellite or Integrated Services Digital Network lines with a theoretical bandwidth of 384 Kb/s. They showed the tele-echography system helped to identify 66% of lesions and 83% of symptomatic pathologies.
Trust, but Verify: Optimistic Visualizations of Approximate Queries for Exploring Big Data (2017)

Analysts need interactive speed for exploratory analysis, but big data systems are often slow. With sampling, data systems can produce approximate answers fast enough for exploratory visualization, at the cost of accuracy and trust. We propose optimistic visualization, which approaches these issues from a user experience perspective. This method lets analysts explore approximate results interactively, and provides a way to detect and recover from errors later. Pangloss implements these ideas. We discuss design issues raised by optimistic visualization systems. We test this concept with five expert visualizers in a laboratory study and three case studies at Microsoft. Analysts reported that they felt more confident in their results, and used optimistic visualization to check that their preliminary results were correct.