gebhart/patrepeval huggingface dataset:
Notch Signaling in Cardiac Development (2008)

The Notch signaling pathway has been demonstrated to play a critical role during mammalian cardiac development based on recent findings from gene-targeted mice. In addition, mutations in the Notch signaling pathway have been associated with human congenital heart defects such as Alagille syndrome, bicuspid aortic valve disease, calcification of the heart valves, and ventricular septal defects. Recently, it was demonstrated that Notch activation in the endocardium regulates ventricular myocardial development and that the Notch downstream target genes Hey1 and Hey2 are required for the establishment of the atrioventricular canal myocardial boundary. The Notch pathway has previously been implicated in regulating endothelial-to-mesenchymal transition during development of the heart valves, and recent reports further dissect the role of individual Notch downstream target genes during this process. In addition, a role for the Notch pathway during cardiac neural crest cell development has been identified, which provides a potential mechanism for the findings seen in Alagille syndrome. This review focuses on recently reported findings that elucidate mechanisms regulated by the Notch pathway during ventricular, atrioventricular canal, and outflow tract development.
High cell density cultivation and recombinant protein production with Escherichia coli in a rocking-motion-type bioreactor (2010)

Rocking-motion-type bioreactors may provide an interesting alternative to standard cultivation in bioreactors for cultivation of bacteria and recombinant protein production. The BIOSTAT Cultibag RM system with the single-use sensors and advanced control system paves the way for the fed-batch technology also to rocking-motion-type bioreactors. It is possible to reach cell densities which are far above shake flasks and typical for stirred tank reactors with the improved oxygen transfer rate. For more simple applications the EnBase Flo method offers an easy and robust solution for rocking-motion-systems which do not have such advanced control possibilities.
Adjuvant immunotherapy of established murine renal cancer by interleukin 2-stimulated cytotoxic lymphocytes. (1986)

We have used a transplantable experimental murine renal carcinoma (Renca) to evaluate the adjuvant immunotherapeutic potential of cytotoxic lymphocytes stimulated by in vitro incubation for 24 h with human recombinant interleukin 2 (rIL-2). The Renca tumor model is therapeutically challenging since, following intrarenal implant, it grows progressively with local invasion and development of spontaneous metastases in abdominal lymph nodes, lungs, and liver. Therefore, successful treatment requires control of both primary tumor, local and regional invasive growth, and systemic metastases. Our studies have shown that rIL-2-stimulated cytotoxic lymphocytes efficiently lyse Renca in vitro. Further, both doxorubicin hydrochloride and an active metabolite of cyclophosphamide also inhibited the growth of Renca in vitro. In vivo administration of doxorubicin hydrochloride, cyclophosphamide or rIL-2-stimulated cytotoxic lymphocytes and rIL-2 to mice bearing established Renca tumors (7-day disease) resulted in a significant (P less than 0.01) increase in short-term survivors (at 45 days), but only 17% cures. However, combination chemoimmunotherapy consisting of doxorubicin hydrochloride and rIL-2-stimulated cytotoxic lymphocytes plus rIL-2 results in the cure of 67% of mice bearing established Renca. These results demonstrate that chemotherapy and immunotherapy with adoptively transferred cytotoxic lymphocytes can function synergistically in the treatment of established murine renal carcinoma.
Content Adaptive Enhancement of Multi-View Depth Maps for Free Viewpoint Video (2010)

Depth map estimation is an important part of the multi-view video coding and virtual view synthesis within the free viewpoint video applications. However, computing an accurate depth map is a computationally complex process, which makes real-time implementation challenging. Alternatively, a simple estimation, though quick and promising for real-time processing, might result in inconsistent multi-view depth map sequences. To exploit this simplicity and to improve the quality of depth map estimation, we propose a novel content adaptive enhancement technique applied to the previously estimated multi-view depth map sequences. The enhancement method is locally adapted to edges, motion and depth-range of the scene to avoid blurring the synthesized views and to reduce the computational complexity. At the same time, and very importantly, the method enforces consistency across the spatial, temporal and inter-view dimensions of the depth maps so that both the coding efficiency and the quality of the synthesized views are improved. We demonstrate these improvements in the experiments, where the enhancement method is applied to several multi-view test sequences and the obtained synthesized views are compared to the views synthesized using other methods in terms of both numerical and perceived visual quality.
CDAM — Compound Document Access and Management. An Object-Oriented Approach (1992)

This paper describes an object-oriented database approach for a direct access and memory management system which covers the needs of storing compound resp. multimedia documents in a multi-user and distributed environment. Document components may be distributed over several physical locations, documents may share components, and multi-user access is supported. In addition, the model allows to represent much of the document semantics, giving the opportunity to define and access components favourably through their properties. Rapid access and manipulation (using for example, associative methods) as well as encapsulation of data to minimize side effects are also considered.
Newer synthetic peptide substrates in coagulation testing: some practical considerations for automated methods. (1983)

More than 100 chromogenic and fluorogenic peptide substrates are now available for the evaluation of coagulation and related parameters. Many of these substrates exhibit undesirable physical properties, such as insolubility, surface adsorption, and interaction with endogenous plasma proteins. Some of these substrates are capable of inhibiting serine protease generation during activation in the global assay. In order to develop synthetic chromogenic substrates with desirable physical and biochemical characteristics, modified amino acids, such as CHG, CHT, and Nleu, have been utilized. Similarly, to provide a favorable molecular environment to facilitate enzyme and synthetic substrate interactions, various molecular manipulations, such as the introduction of bulky groups, is helpful in developing substrates for protein Ca and C1-esterase. Substrates for Factor Xa, CH3-O-CO-CHG-Arg-pNA (bovine Xa, Km 2.5 X 10(-4) M; human, Km 3.5 X 10(-4) M); thrombin, H-D-CHT-Ala-Arg-pNA (bovine thrombin, Km 3 X 10(-6) M; human thrombin, Km 6 X 10(-6) M); plasmin, H-D-Nleu-CHT-Lys-pNA (human plasmin, Km 2.2 X 10(-5) M) were found to have identical or superior biochemical characteristics to the earlier substrates. These newer substrates were found to be more soluble (greater than 5 X 10(-4) M) in physiologic buffer, less susceptible to autoamidolysis at reaction conditions, and did not produce opacity of the test solution in final concentrations of 5 X 10(-4) M. Comparable results on normal and pathologic plasma samples were obtained in various laboratory assays that utilize currently available substrates for Factors Xa and IIa, kallikrein, and plasmin (R = greater than 0.9). We propose that prior to the application of a new synthetic substrate in a given assay, a careful biochemical and physical screening of the substrate, the assay conditions, and the interaction of substrates with plasma proteins is highly desirable.
Amplitude-preserved wave-equation migration (2001)

We analyze the amplitude variation as a function of reflection angle (AVA) for angle-domain common image gathers (ADCIG) produced via wave-equation migration. Straightforward implementations of the two main ADCIG methods lead to contradictory, thus inaccurate, amplitude responses. The amplitude inaccuracy is related to the fact that downward-continuation migration is the adjoint of upward-continuation modeling, but it is only a poor approximation of its inverse. We derive the frequency-wavenumber domain diagonal weighting operators that make migration a good approximation to the inverse of modeling. With these weights, both ADCIG methods produce consistent results. The main applications that follow from this paper are true-amplitude migration and pseudounitary modeling/migration, usable for iterative inversion. The two most important factors that degrade the accuracy of wave-equation ADCIGs are the limited sampling and offset range, combined with the band-limited nature of seismic data.
Sequence analysis of the major outer membrane protein gene of Chlamydia pneumoniae (1991)

Compared with the major outer membrane proteins (MOMPs) of the other chlamydial species, the Chlamydia pneumoniae MOMP appears to be less antigenically complex, and as determined by immunoblot analysis, it does not appear to be the immunodominant antigen recognized during infection. Nucleotide sequence analysis of the C. pneumoniae MOMP gene (ompA) revealed that it consisted of a 1,167-base open reading frame with an inferred 39,344-dalton mature protein of 366 amino acids plus a 23-amino-acid leader sequence. A ribosomal-binding site was located in the 5' upstream region, and two stop codons followed by an 11-base dyad forming a stable stem-loop structure were identified. This sequence shares 68 and 71% DNA sequence homology to the Chlamydia trachomatis serovar L2 and Chlamydia psittaci ovine abortion agent MOMP genes, respectively. Interspecies alignment identified regions, corresponding to the variable domains, which share little sequence similarity with the other chlamydial MOMPs. All seven cysteines conserved in the C. trachomatis and C. psittaci MOMPs, which are involved in the formation of disulfide cross-linkages, are found in the C. pneumoniae MOMP.
Phonetically-based vector excitation coding of speech at 3.6 kbps (2003)

A phonetically based segmentation of speech is performed to classify segments into five classes: onset, unvoiced low-pass voiced, steady-state voiced, and transient voiced. The segment lengths are constrained to an integer multiple of a unit-frame. For each segment class, a distinctive coding scheme based on vector excitation coding (VXC) is used. The maximum bit-rate is 3.6 kb/s, and a moderate coding delay of 45 ms is incurred. Performance is roughly comparable to conventional VXC/CELP (code-excited linear prediction) coding at 4.8 kb/s.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Modulation of the Inflammatory Properties and Hepatotoxicity of Recombinant Adenovirus Vectors by the Viral E4 Gene Products (2000)

Liver toxicity and inflammation were assessed in C57BL/6, CBA, and BALB/c mice injected intravenously with a series of recombinant adenoviruses deleted simultaneously in E1/E3, in E1/E3/E2A, or in E1/E3/E4. All vectors were either devoid of transgenes or carried in E1 the human CFTR cDNA under the control of the CMV promoter. Injection of the E1/E3-deleted vector induced a significant liver dystrophy and inflammatory responses that were accompanied by an increased serum transaminase concentration. The vector toxicity remained elevated on additional deletion of the E2A gene and was further enhanced when hCFTR was expressed. In contrast, additional deletion of E4 led to a reduction in hepatotoxicity, suggesting an active role of E4 gene products in liver injury. However, deletion of E4 also led to a loss of transgene expression. To identify the individual E4 product(s) involved in liver toxicity and in the regulation of transgene expression, a series of isogenic E1/E3-deleted vectors, with or without the hCFTR transgene, and containing various combinations of functional E4 open reading frames (ORFs), were evaluated in vitro and in vivo. We demonstrate that liver injury was markedly reduced with vectors containing either ORF3 alone or ORF3,4 while vectors containing ORF4, ORF6,7 or ORF3,6,7 still displayed elevated hepatotoxicity and inflammatory responses. Moreover, transgene expression was restored when ORF3,4 or ORF3,6,7 was retained in the vector. These results highlight the importance of the E4 gene products in the design of improved in vivo gene transfer vectors.
THE LITHIUM TOKAMAK EXPERIMENT (LTX) AND LOW-RECYCLING SPHERICAL TOKAMAK REACTORS (2009)

First Page
Genome editing with RNA-guided Cas9 nuclease in Zebrafish embryos (2013)

Recent advances with the type II clustered regularly interspaced short palindromic repeats (CRISPR) system promise an improved approach to genome editing. However, the applicability and efficiency of this system in model organisms, such as zebrafish, are little studied. Here, we report that RNA-guided Cas9 nuclease efficiently facilitates genome editing in both mammalian cells and zebrafish embryos in a simple and robust manner. Over 35% of site-specific somatic mutations were found when specific Cas/gRNA was used to target either etsrp, gata4 or gata5 in zebrafish embryos in vivo. The Cas9/gRNA efficiently induced biallelic conversion of etsrp or gata5 in the resulting somatic cells, recapitulating their respective vessel phenotypes in etsrp(y11) mutant embryos or cardia bifida phenotypes in fau(tm236a) mutant embryos. Finally, we successfully achieved site-specific insertion of mloxP sequence induced by Cas9/gRNA system in zebrafish embryos. These results demonstrate that the Cas9/gRNA system has the potential of becoming a simple, robust and efficient reverse genetic tool for zebrafish and other model organisms. Together with other genome-engineering technologies, the Cas9 system is promising for applications in biology, agriculture, environmental studies and medicine.
Heparin-induced thrombocytopenia/thrombosis in a transgenic mouse model requires human platelet factor 4 and platelet activation through FcγRIIA (2001)

Heparin-induced thrombocytopenia/thrombosis (HIT/HITT) is a severe, life-threatening complication that occurs in 1% to 3% of patients exposed to heparin. Interactions between heparin, human platelet factor 4 (hPF4), antibodies to the hPF4/heparin complex, and the platelet Fc receptor (FcR) for immunoglobulin G, FcgammaRIIA, are the proposed primary determinants of the disease on the basis of in vitro studies. The goal of this study was to create a mouse model that recapitulates the disease process in humans in order to understand the factors that predispose some patients to develop thrombocytopenia and thrombosis and to investigate new therapeutic approaches. Mice that express both human platelet FcgammaRIIA and hPF4 were generated. The FcgammaRIIA/hPF4 mice and controls, transgenic for either FcgammaRIIA or hPF4, were injected with KKO, a mouse monoclonal antibody specific for hPF4/heparin complexes, and then received heparin (20 U/d). Nadir platelet counts for KKO/heparin-treated FcgammaRIIA/hPF4 mice were 80% below baseline values, significantly different (P <.001) from similarly treated controls. FcgammaRIIA/hPF4 mice injected with KKO and 50 U/d heparin developed shock and showed fibrin-rich thrombi in multiple organs, including thrombosis in the pulmonary vasculature. This is the first mouse model of HIT to recapitulate the salient features of the human disease and demonstrates that FcgammaRIIA and hPF4 are both necessary and sufficient to replicate HIT/HITT in an animal model. This model should facilitate the identification of factors that modulate disease expression and the testing of novel therapeutic interventions.
Human papillomavirus as a risk factor for the increase in incidence of tonsillar cancer (2006)

Smoking and alcohol are well-known etiological factors in tonsillar cancer. However, as in cervical cancer, human papillomavirus (HPV) is currently found in a sizable proportion of tonsillar cancer. Recent reports from the U.S. and Finland show an increase in the incidence of tonsillar cancer, without a parallel rise in smoking and alcohol consumption. This study investigates whether the incidence of tonsillar cancer has also changed in Sweden and whether a possible explanation of the increase is a higher proportion of HPV-positive tonsillar cancer. The incidence of tonsillar cancer between 1970 and 2002 in the Stockholm area was obtained from the Swedish Cancer Registry. In parallel, 203 pretreatment paraffin-embedded tonsillar cancer biopsies taken during 1970-2002 from patients in the Stockholm area were tested for presence of HPV DNA by PCR. The incidence of tonsillar cancer increased 2.8-fold (2.6 in men and 3.5 in women) from 1970 to 2002. During the same period, a significant increase in the proportion of HPV-positive tonsillar cancer cases was observed, as it increased 2.9-fold (p < 0.001). The distribution of HPV-positive cases was 7/30 (23.3%) in the 1970s, 12/42 (29%) in the 1980s, 48/84 (57%) in the 1990s and 32/47 (68%) during 2000-2002. We have demonstrated a highly significant and parallel increase both in the incidence of tonsillar cancer and the proportion of HPV-positive tumors. Hence, HPV may play an important role for the increased incidence of tonsillar cancer. This should definitely influence future preventive strategies as well as treatment for this type of cancer.
Nuclear roundness factor. A predictor of progression in untreated stage A2 prostate cancer (1984)

A measurement of nuclear roundness involving computer-assisted image analysis of histologic specimens was used to predict the prognosis of 19 patients with Stage A2 prostate cancer. This technique accurately identified those tumors that clinically progressed without treatment and those that did not, in contrast to the Gleason grading system, which produced significant prognostic overlap. What separated most of these tumors was the quantification and degree of irregularity of a relatively small subpopulation of cancer nuclei among a majority of rounder nuclei. There are currently several practical limitations in the use of this method, but with improvements in technique and in methods of obtaining tissue, computerized image analysis of nuclear shape may become a valuable tool for analyzing prostate cancer in a quantitative manner, thereby providing valuable information relative to the prognosis of the individual patient.
Analysis of risk factors that may be associated with progression from ocular hypertension to primary open angle glaucoma (2002)

Patients who have OHT may be at higher risk of developing POAG if they also have myopia, a family history of glaucoma or are of older age.
Surfactant Proteins A and D Suppress Alveolar Macrophage Phagocytosis via Interaction with SIRPα (2008)

SP-A and SP-D tonically inhibit alveolar macrophage phagocytosis by binding SIRP alpha. During acute pulmonary inflammation, defects in apoptotic cell clearance are overcome by recruited mononuclear phagocytes.
Giving centre stage to top-down inhibitory mechanisms for selective attention (2020)

Selective attention determines the sensory signals that are processed at higher levels at the expense of others and is biased by higher-order brain regions which anticipate task-relevant stimuli and increase neural sensitivity to them in the sensory cortex. Often, this is thought to occur through excitation of selected neurons, but some studies have suggested that it is not the full description of the process. Increasingly, evidence has pointed to an alternative, top-down inhibitory biasing mechanism. Here, we investigated such an inhibitory model of attention. We first showed how sensitivity to stimulus features known to be task-irrelevant are reduced through top-down suppression. Secondly, we demonstrated a biologically grounded spiking model’s ability to modulate information processing and benchmarked it to physiology. Lastly, we explored the interaction between the excitatory and inhibitory models of top-down attention in a foraging agent. Our results support the inhibitory model of top-down attention as a biological attentional mechanism and show how it fits into the current zeitgeist of top-down attentional mechanisms.
Insulin delivery by somatic cell gene therapy (1993)

The feasibility of somatic cell gene therapy as a method of insulin delivery has been studied in mice. Murine pituitary AtT20 cells were transfected with a human preproinsulin DNA in a plasmid containing a metallothionein promoter and a gene conferring resistance to the antibiotic G418. The AtT20MtIns-1.4 clone of cells was selected because of its higher insulin-releasing activity compared with other clones. After culturing for 24 h in Dulbecco's medium containing 10 mM glucose, the AtT20MtIns-1.4 cells released human insulin at about 5 ng/10(6) cells per 24 h. Insulin release was not significantly altered by raised concentrations of glucose, potassium or calcium, but insulin release was increased by 20 mM arginine, 5 mM isomethylbutylxanthine and 90 microM zinc. AtT20MtIns-1.4 cells (2 x 10(6)) were implanted intraperitoneally into non-diabetic athymic nude (nu/nu) mice, and the mice were made diabetic by injection of streptozotocin after 7 days. Release of human insulin in vivo was assessed using a specific plasma human C-peptide assay. Human C-peptide concentrations were maintained at about 0.1 pmol/ml throughout the 29 days of the study. The development of streptozotocin-induced hyperglycaemia was delayed in recipients of the cells releasing human insulin, compared with a control group receiving an implant of non-transfected cells. At autopsy the implanted AtT20MtIns-1.4 cells in each recipient had formed a tumour-like aggregation, with an outer region of insulin-containing cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Differential Requirements for LFA-1 Binding to ICAM-1 and LFA-1-Mediated Cell Aggregation (1998)

Cellular adhesion through the beta2 integrin lymphocyte function-associated Ag (LFA)-1 is a complex event involving activation, ligand binding, and cell shape changes that ultimately result in enhanced adhesion. In this report we define requirements for ligand binding and post receptor signaling by comparing two mechanisms of activation of LFA-1: 1) inside-out signaling and 2) direct activation by the beta2 Ab, CBR LFA-1/2. Our results demonstrate that activation of LFA-1 binding to ICAM-1 by CBR LFA-1/2, in contrast to inside-out signaling mechanisms, does not require protein kinase C activation or protein phosphatase 2A activity nor is it affected by agents that interfere with reorganization of the cytoskeleton. Inhibition of protein tyrosine kinase activity does not affect ICAM- binding by either mechanism of activation. However, activation by either mode does require the presence of the beta cytoplasmic domain; deletion of the C-terminal phenylalanine or the five amino acid stretch between 756-762 abolished activation of LFA-1. This, combined with the observation that intracellular energy pools must be preserved, implicates the beta cytoplasmic domain in a key energy-dependent conformational change in LFA-1 that is required to achieve enhanced ligand binding. Post ligand binding events induced by both PMA and Ab stimulation, as measured by homotypic aggregation, require protein tyrosine kinase, phosphatase, and RhoA activities. By examining both ligand binding and aggregation, we have been able to dissect the signaling components critical in the multistep process of LFA-1-mediated cellular adhesion.
X Y Z System of Producing Hybrid Wheat<sup>1</sup> (1972)

A chromosomal recessive male‐sterility factor and a corresponding fertility factor on a homoeologous alien chromosome make available a system of producing hybrid wheat, Triticum aestivum L. era. Thell. Three lines, X, Y, and Z, are homozygous for the male‐sterility factor and contain 2, 1, and 0 doses of the alien chromosome, respectively. Limited roguing of plants possessing an alien trait is involved in the first stage only. Acquisition of required genetic stocks appears feasible.