gebhart/patrepeval huggingface dataset:
Optimal radiographic magnification for portal imaging (1994)

Two approaches to estimate the optimal radiographic magnification for a TV camera-based portal imaging system and portal films have been used. The first approach optimizes signal transfer while the second optimizes signal-to-noise ratio (SNR) transfer. In order to perform these optimization calculations, the physical characteristics of the imaging system (modulation transfer function and noise power spectrum) as well as the sizes of the radiation sources of our medical linear accelerators have been measured. Using these data, the optimal magnification considering signal transfer alone (M signal) has been calculated to range between 2.0 and 2.3 for the TV camera-based imaging system and is about 1.0 for portal films. Conversely, the optimal magnification considering SNR transfer (MSNR) has been calculated to range between 1.5 and 1.7 for the TV camera-based imaging system and is about 1.0 for portal films. The results suggest that most portal imaging systems are operated close to their optimal radiographic magnification.
Method for the Comparative Glycomic Analyses of O-Linked, Mucin-Type Oligosaccharides (2004)

A method is presented for the direct relative quantitation of distinct O-linked mucin-type oligosaccharides. Mucin-type oligosaccharides are found in a host of tissues from anuran to humans. Because they are often associated with extracellular matrix, they play important roles in cell-cell recognition. Changes in glycosylation of O-linked oligosaccharides are associated with diseases such as cancer. In fertilization, they play an active role in sperm-egg recognition. We describe a method for observing changes in glycosylation of mucin-type oligosaccharides by incorporating deuterium in the release procedure. Oligosaccharides from two different sources are released separately by sodium tetrahydroborate and sodium tetradeuterioborate. The oligosaccharides are combined and separated into components by HPLC. By observing the ratio of deuterated and undeuterated species, changes in glycosylation are precisely quantified. This method is illustrated with mucin-type oligosaccharides from the egg jelly coat of the anuran Xenopus laevis.
General pharmacological studies on 5,8,11,14,17-eicosapentaenoic acid ethyl ester(EPA-E). (1989)

EPA-E, even at 3,000 mg/kg, p.o., did not affect the general behaviors, spontaneous locomotor activities, pentobarbital hypnosis and body temperature; and it did not elicit anticonvulsant, analgesic and muscle relaxant actions. It had no influence on spontaneous EEG activities, even at 3,000 mg/kg, i.d. EPA-E at concentrations up to 10(-4) M, did not affect the tonus or agonist-induced contraction of the isolated ileum, trachea, fundus and vas deferens. EPA-E had no influence on the spontaneous movement of isolated ileum or uterus. EPA-E did not affect the nictitating membrane contraction and intestinal propulsive motility, and it did not damage gastric mucosa nor elicit antiulcer action. EPA-E at 1,000 mg/kg were without effect on gastric secretory volume (SV), total acidity (TA) and pepsin activities (PA). However, EPA-E at 3,000 mg/kg significantly decreased SV and TA without significantly decreasing PA. EPA-E caused no changes in the respiration, blood pressure, heart rate and ECG at the doses up to 3,000 mg/kg; and it did not affect the heart rate and contractile force on the isolated atria at concentrations up to 10(-4) M. The intracutaneous injection of 2.0% EPA-E produced neither anesthetic nor irritative action. EPA-E did not elicit hemolytic action at 10(-4) M. EPA-E, even at 3,000 mg/kg, did not affect the neuro-muscular transmission, urine volume, urinary excretion of electrolytes and carrageenin edema. These results suggested that EPA-E has no noticeable effects on the central nervous, autonomic nervous, respiratory and cardiovascular systems and so on.
Mapping proteins to disease terminologies: from UniProt to MeSH (2008)

This study is a first attempt to link proteins in UniProtKB to the medical resources. The indexing we provided will help clinicians and researchers navigate from diseases to genes and from genes to diseases in an efficient way. The mapping is available at: http://research.isb-sib.ch/unimed.
Direct Cellular Lysis/Protein Extraction Protocol for Soil Metaproteomics (2010)

We present a novel direct protocol for deep proteome characterization of microorganisms in soil. The method employs thermally assisted detergent-based cellular lysis (SDS) of soil samples, followed by TCA precipitation for proteome extraction/cleanup prior to liquid chromatography-mass spectrometric characterization. This approach was developed and optimized using different soils inoculated with genome-sequenced bacteria (Gram-negative Pseudomonas putida or Gram-positive Arthrobacter chlorophenolicus). Direct soil protein extraction was compared to protein extraction from cells isolated from the soil matrix prior to lysis (indirect method). Each approach resulted in identification of greater than 500 unique proteins, with a wide range in molecular mass and functional categories. To our knowledge, this SDS-TCA approach enables the deepest proteome characterizations of microbes in soil to date, without significant biases in protein size, localization, or functional category compared to pure cultures. This protocol should provide a powerful tool for ecological studies of soil microbial communities.
Noradrenergic-Specific Transcription of the Dopamine β-Hydroxylase Gene Requires Synergy of MultipleCis-Acting Elements Including at Least Two Phox2a-Binding Sites (1998)

Dopamine β-hydroxylase (DBH) catalyzes the conversion of dopamine to noradrenaline and is selectively expressed in noradrenergic and adrenergic neurons and neuroendocrine cells. Recent data from this laboratory showed that a paired-like homeodomain (HD) protein, Phox2a, interacts with the HD-binding site residing within a composite promoter of the human DBH gene, designated domain IV, in a cell-specific manner and directly controls noradrenergic-specific DBH promoter activity. In this report, we demonstrate that three additional protein-binding sites (i.e., domains I, II, and III) between domain IV and the TATA box are critical for intact DBH promoter activity in noradrenergic cells and that they activate DBH transcription in a highly concerted manner. Transient transfection assays of mutant DBH reporter constructs indicated that domain I was active in every cell line tested, whereas domain III was preferentially active in DBH-positive cells. Remarkably, mutation of domain II was associated with inactivation of DBH promoter activity exclusively in DBH-positive cell lines, defining it as another noradrenergic-specific promoter element. The cell-specific profile of the promoter function of these sequence motifs was further supported by in vitro DNA-binding studies and Southwestern analysis. Furthermore, competition and antibody supershift assays show that transcription factors Sp1 and AP2 are the cognate nuclear factors interacting with domains I and III, respectively. Parallel evidence indicates that domain II is another Phox2a-binding site, demonstrating at least two binding sites for this factor in the upstream DBH promoter. Strikingly, four tandem copies of domain II increased the promoter activity of a minimal DBH promoter by 100- to 200-fold in DBH-positive cell lines without compromising cell specificity. Cotransfection of Phox2a-expression vector dramatically increased the activity of the multiple domain II promoter only in DBH-negative cell lines, confirming that domain II is responsive to Phox2a. Collectively, this study emphasizes a critical role of Phox2a as well as its functional synergism with other transcription factors (e.g., CREB, AP2, and Sp1) in transcriptional activation of the DBH gene.
Silicon Nanowire Radial p−n Junction Solar Cells (2008)

We have demonstrated a low-temperature wafer-scale etching and thin film deposition method for fabricating silicon n-p core-shell nanowire solar cells. Our devices showed efficiencies up to nearly 0.5%, limited primarily by interfacial recombination and high series resistance. Surface passivation and contact optimization will be critical to improve device performance in the future.
Potent, Brain-Penetrant, Hydroisoindoline-Based Human Neurokinin-1 Receptor Antagonists (2009)

3-[(3aR,4R,5S,7aS)-5-{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy}-4-(4-fluorophenyl)octahydro-2H-isoindol-2-yl]cyclopent-2-en-1-one (17) is a high affinity, brain-penetrant, hydroisoindoline-based neurokinin-1 (NK(1)) receptor antagonist with a long central duration of action in preclinical species and a minimal drug-drug interaction profile. Positron emission tomography (PET) studies in rhesus showed that this compound provides 90% NK(1) receptor blockade in rhesus brain at a plasma level of 67 nM, which is about 10-fold more potent than aprepitant, an NK(1) antagonist marketed for the prevention of chemotherapy-induced and postoperative nausea and vomiting (CINV and PONV). The synthesis of this enantiomerically pure compound containing five stereocenters includes a Diels-Alder condensation, one chiral separation of the cyclohexanol intermediate, an ether formation using a trichloroacetimidate intermediate, and bis-alkylation to form the cyclic amine.
A Collision Probability Model of Portal Vein Tumor Thrombus Formation in Hepatocellular Carcinoma (2015)

Hepatocellular carcinoma is one of the most common malignancies worldwide, with a high risk of portal vein tumor thrombus (PVTT). Some promising results have been achieved for venous metastases of hepatocellular carcinoma; however, the etiology of PVTT is largely unknown, and it is unclear why the incidence of PVTT is not proportional to its distance from the carcinoma. We attempted to address this issue using physical concepts and mathematical tools. Finally, we discuss the relationship between the probability of a collision event and the microenvironment of the PVTT. Our formulae suggest that the collision probability can alter the tumor microenvironment by increasing the number of tumor cells.
Mutational Analysis of the p53 Core Domain L1 Loop (2006)

The p53 tumor suppressor gene acquires missense mutations in over 50% of human cancers, and most of these mutations occur within the central core DNA binding domain. One structurally defined region of the core, the L1 loop (residues 112-124), is a mutational "cold spot" in which relatively few tumor-derived mutations have been identified. To further understand the L1 loop, we subjected this region to both alanine- and arginine-scanning mutagenesis and tested mutants for DNA binding in vitro. Select mutants were then analyzed for transactivation and cell cycle analysis in either transiently transfected cells or cells stably expressing wild-type and mutant proteins at regulatable physiological levels. We focused most extensively on two p53 L1 loop mutants, T123A and K120A. The T123A mutant p53 displayed significantly better DNA binding in vitro as well as stronger transactivation and apoptotic activity in vivo than wild-type p53, particularly toward its pro-apoptotic target AIP1. By contrast, K120A mutant p53, although capable of strong binding in vitro and wild-type levels of transactivation and apoptosis when transfected into cells, showed impaired activity when expressed at normal cellular levels. Our experiments indicate a weaker affinity for DNA in vivo by K120A p53 as the main reason for its defects in transactivation and apoptosis. Overall, our findings demonstrate an important, yet highly modular role for the L1 loop in the recognition of specific DNA sequences, target transactivation, and apoptotic signaling by p53.
Population Growth of the Floating Weed Salvinia molesta: Field Observation and a Global Model Based on Temperature and Nitrogen (1986)

P. M. Room, P. A. Thomas, Population Growth of the Floating Weed Salvinia molesta: Field Observation and a Global Model Based on Temperature and Nitrogen, Journal of Applied Ecology, Vol. 23, No. 3 (Dec., 1986), pp. 1013-1028
Fc RECEPTORS AND THEIR INTERACTIONS WITH IMMUNOGLOBULINS (1996)

Receptors for the Fc domain of immunoglobulins play an important role in immune defense. There are two well-defined functional classes of mammalian receptors. One class of receptors transports immunoglobulins across epithelial tissues to their main sites of action. This class includes the neonatal Fc receptor (FcRn), which transports immunoglobulin G (IgG), and the polymeric immunoglobulin receptor (pIgR), which transports immunoglobulin A (IgA) and immunoglobulin M (IgM). Another class of receptors present on the surfaces of effector cells triggers various biological responses upon binding antibody-antigen complexes. Of these, the IgG receptors (Fc gamma R) and immunoglobulin E (IgE) receptors (Fc epsilon R) are the best characterized. The biological responses elicited include antibody-dependent, cell-mediated cytotoxicity, phagocytosis, release of inflammatory mediators, and regulation of lymphocyte proliferation and differentiation. We summarize the current knowledge of the structures and functions of FcRn, pIgR, and the Fc gamma R and Fc epsilon RI proteins, concentrating on the interactions of the extracellular portions of these receptors with immunoglobulins.
Assessment of primary hemostasis by PFA-100 analysis in a tertiary care center. (2000)

We evaluated the utility of the PFA-100 platelet function analyzer in identifying disorders in platelet function and/or von Willebrand factor (vWF) in patients with various systemic disorders being followed at a tertiary care center. Closure times were determined with collagen/ ADP (CADP) and collagen/epinephrine (CEPI) cartridges for 305 patients, and abnormal results were further evaluated with platelet aggregometry and vWF analysis. Prolonged CADP and/or CEPI closure times were identified in 114 patients (37.3%), but most were isolated prolonged CEPI closure times predominantly due to aspirin therapy (79 patients). Prolonged CADP closure times were most frequently due to qualitative platelet defects and/or decreased vWF levels. Prolonged CADP closure times were encountered most frequently in patients with sickle cell disease and were associated with a decreased hematocrit. This study demonstrated that the PFA-100 analyzer can accurately assess vWF-dependent platelet function and detect other platelet defects under high shear stress in complex patient populations.
Acoustic imaging for nondestructive evaluation (1979)

The application of acoustic imaging techniques to non-destructive testing (NDT) of materials is discussed. After a description of the standard NDT techniques employed in the field and some examples of mechanically scanned imaging devices, most of the paper is devoted to a description of electronically scanned and focused systems. As holographic techniques are described by Ahmed et al. [22] in an accompanying paper, they are not discussed here. It is shown that the use of imaging techniques makes it possible to locate the position of flaws quickly and accurately.
Absence of compensatory platelet activation in patients with severe haemophilia, but evidence for a platelet collagen-activation defect (2002)

Severe haemophilia is a serious, haemorrhagic disorder of the plasmatic coagulation system. In this study we investigated, whether 'compensatory' activation of the platelet coagulation system occurs in this situation. Platelet function was investigated with aggregation, adhesion and flow cytometric assays. In addition, we performed clot and platelet plug formation tests and determined endogenous thrombin potentials in patients with severe haemophilia A or B; results were compared to those of healthy controls. Platelet aggregation in response to stimulation with ADP, ristocetin and epinephrine was similar in patients and controls; aggregation in response to collagen was reduced significantly in haemophiliacs. Flow cytometric analysis of P-selectin (CD 62P) and CD 63, of the conformationally changed GP IIb/IIIa with PAC 1 and of thrombospondin bound to CD 36 (GP IV) was performed at baseline and post stimulation. Baseline expression of all markers was similar in haemophiliacs and controls. After stimulation of the platelet thrombin receptors with the thrombin receptor activating peptide (TRAP) 6, the surface expression of all markers increased significantly; again, the expression was similar in haemophiliacs and controls. With thrombelastography and PFA 100 analysis, clot formation under low shear and platelet plug formation under high shear is measured. Both test results revealed a significantly reduced clot and platelet plug formation capacity in severe haemophiliacs. Our results did not reveal signs of enhanced platelet preactivation in haemophiliacs, indicating that baseline platelet reactivity in severe haemophilia remains in a neutral state, despite the severely haemorrhagic condition. As expected, both thrombin and clot formation capacities were impaired significantly in severe haemophilia. The reduced response to collagen-based platelet stimulation tests is indicative of a concomitant platelet function defect. This defect probably contributes to the intensity of bleeding events in patients with severe haemophilia.
A Gd3Al tetranuclear complex as a potential bimodal MRI/optical imaging agent (2012)

A new self-assembled gadolinium(III)-aluminum(III) complex (Gd(3)Al) was synthesized and characterized. The efficacy of this Gd(3)Al complex as a potential bimodal magnetic resonance imaging (MRI)/optical imaging agent has been evaluated. Relaxivity studies showed that the Gd(3)Al complex has higher relaxation efficiency (7.18 mM(-1) s(-1)) compared with the clinically used complex gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA, 3.9 mM(-1) s(-1)) at 400 MHz and 25 °C. In vitro T(1)-MR images on a 0.5 T magnetic field exhibited a remarkable enhancement of signal contrast for Gd(3)Al compared to Gd-DTPA. Furthermore, the Gd(3)Al complex exhibits bright-green luminescence with the emission spectrum centred at 510 nm. Live-cell fluorescence imaging reveals that the Gd(3)Al complex is permeable to cells and localizes to the cytoplasm. In view of the relaxometric and luminescent properties, this Gd(3)Al complex could serve as a potential bimodal MRI/optical imaging agent.
Layer‐by‐Layer Deposition of Polyelectrolytes—A Versatile Tool for the In Vivo Repair of Blood Vessels (2004)

Layer-by-layer adsorption of polygenic polyelectrolytes is a promising method of treatment in which multilayers are formed on the inner arterial wall (see scheme). An advantage of this technique, which has already proved successful in animal models, is that it is very simple to apply, in contrast to in situ polymerization, which requires irradiation with UV light. Furthermore, it is rapid and allows the incorporation of active drugs in the layer.
The effect of oxygen tension on human articular chondrocyte matrix synthesis: Integration of experimental and computational approaches (2014)

Significant oxygen gradients occur within tissue engineered cartilaginous constructs. Although oxygen tension is an important limiting parameter in the development of new cartilage matrix, its precise role in matrix formation by chondrocytes remains controversial, primarily due to discrepancies in the experimental setup applied in different studies. In this study, the specific effects of oxygen tension on the synthesis of cartilaginous matrix by human articular chondrocytes were studied using a combined experimental-computational approach in a "scaffold-free" 3D pellet culture model. Key parameters including cellular oxygen uptake rate were determined experimentally and used in conjunction with a mathematical model to estimate oxygen tension profiles in 21-day cartilaginous pellets. A threshold oxygen tension (pO2 ≈ 8% atmospheric pressure) for human articular chondrocytes was estimated from these inferred oxygen profiles and histological analysis of pellet sections. Human articular chondrocytes that experienced oxygen tension below this threshold demonstrated enhanced proteoglycan deposition. Conversely, oxygen tension higher than the threshold favored collagen synthesis. This study has demonstrated a close relationship between oxygen tension and matrix synthesis by human articular chondrocytes in a "scaffold-free" 3D pellet culture model, providing valuable insight into the understanding and optimization of cartilage bioengineering approaches.
Cell-dependent efficiency of reiterated nuclear signals in a mutant simian virus 40 oncoprotein targeted to the nucleus. (1988)

We investigated the requisites for, and functional consequences of, the relocation to the nucleus of a transforming nonkaryophilic mutant of the simian virus 40 large T antigen (a natural deletion mutant lacking an internal large-T-antigen domain that includes the signal for nuclear transport). Synthetic oligonucleotides were used to obtain gene variants with one or more copies of the signal-specifying sequence inserted near the gene 3' end, in a region dispensable for the main large-T-antigen functions. The analysis of stable transfectant populations showed that mouse NIH 3T3 cells, rat embryo fibroblasts, and simian CS cells (a subclone of CV1 cells) differed considerably in their ability to localize some variant molecules into the nucleus. CS cells were always the most efficient, and NIH 3T3 cells were the least efficient. The nuclear localization improved either with reiteration of the signal or with a left-flank modification of the signal amino acid context. Three signals appeared to be necessary and sufficient, even in NIH 3T3 cells, to obtain a nuclear accumulation comparable to that of wild-type simian virus 40 large T antigen; other signal-cell combinations caused a large variability in subcellular localization among cells of the same population, as if the nuclear uptake of some molecules depended on individual cell states. The effect of the modified location on the competence of the protein to alter cell growth was examined by comparing the activity of variants containing either the normal signal or a signal with a mutation (corresponding to large-T-antigen amino acid 128) that prevented nuclear transport. It was found that the nuclear variant was slightly more active than the cytoplasmic variants in rat embryo fibroblasts and NIH 3T3 cells and was notably less active in CS cells.
Differential effects of levodopa on dopaminergic function in early and advanced Parkinson's disease (1997)

The effect of levodopa on L-[11C]DOPA influx rate was evaluated in patients with early and advanced Parkinson's disease (PD) by using positron emission tomography (PET). The patients were scanned both drug-free and after a subsequent therapeutic levodopa infusion. Regional analysis of striatal L-[11C]DOPA influx rate showed a correlation to the degenerative loss of nerve terminals reported at postmortem analysis in PD. Levodopa induced markedly differential effects on the striatal L-[11C]DOPA influx rate in early and advanced patients. In patients with mild PD, levodopa infusion decreased L-[11C]DOPA influx, whereas in patients with advanced PD, levodopa induced significant upregulation of L-[11C]DOPA influx. These changes were confined to the putamen and were, in both patient categories, most prominent in the dorsal part of the region. The present investigation demonstrates a marked shift in the modulatory action of levodopa with the advancement of PD and suggests the induction of positive feedback in advanced PD. These findings could help explain the less graded clinical response to levodopa in advanced PD and would thus have importance for the understanding of the pathogenesis underlying motor fluctuations.