gebhart/patrepeval huggingface dataset:
Amorphous-SiC thin-film p-i-n light-emitting diode using amorphous-SiN hot-carrier tunneling injection layers (1989)

An approach to improve the luminosity of hydrogenated amorphous silicon carbide (a-SiC:H)-based thin-film visible light-emitting diodes is discussed. High bandgap near-stoichiometric hydrogenated amorphous silicon nitride (a-SiN:H) is utilized as a hot-carrier tunneling injection layer. An improvement of both carrier injection efficiency and luminosity is observed. Technical data on the new approach for carrier injection and on the recombination mechanism are presented. Preliminary results are also presented on the photoluminescence and electroluminescence properties of a-SiC:H/a-SiN:H multilayers.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Ultrastructural features of apoptosis. (1994)

Apoptosis is a gene-directed physiological and programmed process of cell deletion aimed at the regulation of tissue and organ development. It affects different cell types and is triggered by a variety of stimuli all inducing closely comparable structural changes. Despite the deeply different morphology and metabolism of the cell models and the various inducers and their initial effects, a convergence seems to take place in a common metabolic pathway that, in most cases, involves the activation of a Ca2+ dependent endonuclease. A growing body of data is now available on the molecular events that lead to DNA damage. DNA cleavage in nucleosomic or oligonucleosomic fragments is related to the appearance of unusual and very characteristic ultrastructural changes. The nucleus is especially affected, and shows chromatin rearrangements consisting of cup-shaped marginations, sharply separated from diffuse chromatin areas. Nuclear fragmentation subsequently appears, finally followed by the formation of numerous micronuclei. Cytoplasmic damage appears at a very late stage and the process takes place despite good preservation of plasma membrane and cytoplasm.
Urinary Neutrophil Gelatinase Associated Lipocalin (NGAL), a Marker of Tubular Damage, is Increased in Patients with Chronic Heart Failure (2008)

Renal impairment, as measured by reduced glomerular filtration rate (GFR) and increased urinary albumin excretion (UAE), is prevalent in patients with chronic heart failure (CHF) and is associated with reduced survival. The prevalence of structural tubular damage in CHF is unknown. We investigated 90 CHF patients and 20 age and sex matched healthy controls, and determined estimated GFR, UAE, N terminal-pro brain natriuretic peptide (NT-proBNP) and urinary neutrophil gelatinase associated lipocalin (NGAL) as a marker for tubular damage. CHF patients had significantly lower averaged estimated GFR (64+/-17 vs 90+/-12 mL/min/1.73 m(2), P<0.0001), but higher NT-proBNP and UAE levels (both P<0.0001). Median urinary NGAL levels were markedly increased in CHF patients compared to controls (175 (70-346) vs 37 (6-58) microg/gCr, P<0.0001). Both serum creatinine (r=0.26, P=0.006) and eGFR (r=-0.29, P=0.002) were significantly associated with urinary NGAL levels as were NT-proBNP and UAE but to a lesser extent. In conclusion, renal impairment in CHF patients is not only characterised by decreased eGFR and increased UAE, but also by the presence of tubular damage, as measured by increased urinary NGAL concentrations.
Specific bone cells produce DLL4 to generate thymus-seeding progenitors from bone marrow (2015)

Production of the cells that ultimately populate the thymus to generate α/β T cells has been controversial, and their molecular drivers remain undefined. Here, we report that specific deletion of bone-producing osteocalcin (Ocn)-expressing cells in vivo markedly reduces T-competent progenitors and thymus-homing receptor expression among bone marrow hematopoietic cells. Decreased intrathymic T cell precursors and decreased generation of mature T cells occurred despite normal thymic function. The Notch ligand DLL4 is abundantly expressed on bone marrow Ocn(+) cells, and selective depletion of DLL4 from these cells recapitulated the thymopoietic abnormality. These data indicate that specific mesenchymal cells in bone marrow provide key molecular drivers enforcing thymus-seeding progenitor generation and thereby directly link skeletal biology to the production of T cell-based adaptive immunity.
Mechanisms of transactivation by retinoic acid receptors (1993)

Retinoids play an important role in development and differentiation. Their effect is mediated through nuclear receptors, RAR (alpha, beta and gamma) and RXR (alpha, beta and gamma), which are members of a distinct subclass (hereafter referred to as type II) of the nuclear receptor superfamily that includes the thyroid hormone receptor (T3R), the vitamin D3 receptor (VD3R) and the peroxisome proliferator activated receptor (PPAR). Type II receptors transactivate through binding sites composed of closely related half-sites (consensus sequence AGG/TTCA) arranged as direct repeats and, with the possible exception of RXR, do not bind to their cognate binding sites as homodimers but require RXR for high affinity binding. RXR thus provides a link between biologically distinct ligand induced pathways and is a potential target for cross-regulation. In addition, RAR can utilize alternative routes to enhance transcription initiation mediated through transcriptional co-activators which are expressed in a cell-type specific manner.
P2X7Receptor Modulation on Microglial Cells and Reduction of Brain Infarct Caused by Middle Cerebral Artery Occlusion in Rat (2006)

Adenosine 5'-triphosphate outflow increases after an ischemic insult in the brain and may induce the expression of P2X7 receptors in resting microglia, determining its modification into an activated state. To assess the effects of P2X7 receptor blockade in preventing microglia activation and ameliorating brain damage and neurological impairment, we delivered the P2 unselective antagonist Reactive Blue 2 to rats after middle cerebral artery occlusion. In sham-operated animals, devoid of brain damage, double immunofluorescence verified the absence of P2X7 immunoreactivity on resting microglia, astrocytes, and neurons, identified, respectively, by OX-42, glial fibrillary acid protein, and neuronal nuclei (NeuN) immunoreactivity. After ischemia, vehicle-treated rats showed monolateral sensorimotor deficit and tissue damage in striatum and frontoparietal cortex. Moreover, P2X7 immunoreactivity was de novo expressed on activated microglia in infarcted and surrounding areas, as well as on a reactive form of microglia, resting in shape but P2X7 immunoreactive, present in ipsi- and contralateral cingulate and medial frontal cortex. Reactive Blue 2 improved sensorimotor deficit and restricted the volume of infarction, without preventing the expression of P2X7, but inducing it in the microglia of contralateral frontal and parietal cortex and striatum, which had lost reciprocal connections with the remote infarct area. De novo expression of P2X7 occurred in both activated and reactive microglia, suggesting their differentiated roles in the area of infarct and in remote regions. Reactive Blue 2 reduced ischemic brain damage, likely blocking the function of activated microglia in the infarct area, but in the remote brain regions promoted the expression of P2X7 on reactive microglia, developing defense and reparative processes.
A family of eukaryotic lysophospholipid acyltransferases with broad specificity (2007)

The budding yeast ALE1 gene encodes a lysophospholipid acyltransferase (LPLAT) with broad specificity. We show that yeast LPLAT (ScLPLAT) belongs to a distinct protein family that includes human MBOAT1, MBOAT2, MBOAT4, and several closely related proteins from other eukaryotes. We further show that two plant proteins within this family, the Arabidopsis proteins AtLPLAT1 and AtLPLAT2, possess lysophospholipid acyltransferase activities similar to ScLPLAT. We propose that other members of this protein family, which we refer to as the LPLAT family, also are likely to possess LPLAT activity. Finally, we show that ScLPLAT differs from the specific lysophosphatidic acid acyltransferase that is encoded by SLC1 in that it cannot efficiently use lysophosphatidic acid produced by acylation of glycerol-3-phosphate in vitro.
The optical tweezers (2003)

The proposed multiple-point interaction technique realizes direct interaction and control in a virtual environment and presentation. The device for interaction is constructed on the basis of the infrared (IR) laser which is invisible for a human eye and does not interfere with the visual channel of a presentation, since there can be no coincidence of the color of the infrared laser and the visible object on the screen.The special designed optical scheme splits a laser beam into three with a small angle of divergence. As a result we receive the three IR spots on the screen.The coordinates of the laser spots received from the infrared camera are interpreted as a position of the (pointer) cursor after the mathematical processing which is displayed with the help of the projection system and can be interpreted as commands of the application control.
A Serial Analysis of Gene Expression (SAGE) Database Analysis of Chemosensitivity (2004)

Drug sensitivity and resistance has been most extensively studied in cell lines carried in tissue culture. Furthermore, cell lines have been widely used in testing new anticancer agents, despite the widely recognized observation that cell lines are more sensitive to cytotoxic drugs than are their corresponding solid tumors. We used the Serial Analysis of Gene Expression (SAGE) database to identify differences between solid tumors and cell lines, hoping to detect genes that could potentially explain differences in drug sensitivity. SAGE libraries were available for both solid tumors and cell lines from breast, colon, ovarian, pancreatic, and prostate carcinomas and from gliomas and medulloblastomas. Sixty-two genes were identified as overexpressed in tumors. The immune response and complement pathways were the significant common themes, with extracellular matrix (ECM) proteins third. For the 61 genes overexpressed in cell lines, protein synthesis was the dominant theme. We next used the SAGE database to identify genetic differences between tumor types that convey a broad range of survival to the patients that bear them as distant metastases. SAGE gene expression data were correlated with 5-year survivals documented in the SEER (Surveillance, Epidemiology and End-Results) database for patients diagnosed with "distant" or metastatic cancers. These are unlikely to be amenable to surgical resection; therefore, survival here reflects, to some extent, sensitivity to systemic therapy, i.e., chemotherapy. Using survival data as a surrogate of chemotherapy sensitivity, a spectrum can be generated, with testicular cancer at one end and pancreatic cancer at the other. Favorable 5-year survival, despite a distant presentation, correlates with expression of protein synthesis genes. Poor 5-year survival correlates with expression of cell adhesion, cytoskeletal, and ECM genes, a pattern similar to that found to distinguish solid tumors from the more cytotoxin-sensitive cancer cell lines. One interpretation is that resistance to chemotherapy may arise, in part, from the adherent, relatively inert condition (i.e., low in protein synthesis potential) of refractory cancers. Thus, attachment or ECM genes could be targets for anticancer therapy.
Biocompatibility Assessment of Insulating Silicone Polymer Coatings Using an in vitro Glial Scar Assay (2010)

Vapor-deposited silicone coatings are attractive candidates for providing insulation in neuroprosthetic devices owing to their excellent resistivity, adhesion, chemical inertness and flexibility. A biocompatibility assessment of these coatings is an essential part of the materials design process, but current techniques are limited to rudimentary cell viability assays or animal muscle implantation tests. This article describes how a recently developed in vitro model of glial scar formation can be utilized to assess the biocompatibility of vapor-deposited silicone coatings on micron-scale wires. A multi-cellular monolayer comprising mixed glial cells was obtained by culturing primary rat midbrain cells on poly(D-lysine)-coated well plates. Stainless steel microwires were coated with two novel insulating thin film silicone polymers, namely poly(trivinyltrimethylcyclotrisiloxane) (polyV(3)D(3)) and poly(trivinyltrimethylcyclotrisiloxane-hexavinyldisiloxane) (polyV(3)D(3)-HVDS) by initiated chemical vapor deposition (iCVD). The monolayer of midbrain cells was disrupted by placing segments of coated microwires into the culture followed by immunocytochemical analysis after 7 d of implantation. Microglial proximity to the microwires was observed to correlate with the amount of fibronectin adsorbed on the coating surface; polyV(3)D(3)-HVDS adsorbed the least amount of fibronectin compared to both stainless steel and polyV(3)D(3). Consequently, the relative number of microglia within 100 µm of the microwires was least on polyV(3)D(3)-HVDS coatings compared to steel and polyV(3)D(3). In addition, the astrocyte reactivity on polyV(3)D(3)-HVDS coatings was lower compared to stainless steel and polyV(3)D(3). The polyV(3)D(3)-HVDS coating was therefore deemed to be most biocompatible, least reactive and most preferable insulating coating for neural prosthetic devices.
Population Pharmacokinetic Analysis of Panitumumab in Patients With Advanced Solid Tumors (2009)

Panitumumab is a fully human monoclonal antibody targeted to the extracellular domain of human epidermal growth factor receptor (EGFR). A comprehensive population pharmacokinetic model of panitumumab was developed using nonlinear mixed-effects modeling of 1200 patients with advanced solid tumors in 14 clinical studies. The disposition of panitumumab was best described with a 2-compartment model with parallel linear and nonlinear (Michaelis-Menten) elimination pathways. For a typical male patient with colorectal cancer (80 kg, 60 years old), the estimates for the linear clearance (CL), the maximum nonlinear clearance (V(max)/K(m)), the central volume of distribution (V(1)), the peripheral volume of distribution (V(2)), and the Michaelis-Menten constant (K(m)) are 0.273 L/d, 28.4 L/d, 3.95 L, 2.59 L, and 0.426 mcg/mL, respectively. Baseline covariates such as body weight, cancer type, age, sex, and race were studied for their influence on panitumumab pharmacokinetics. Body weight was found to be the most influential covariate on panitumumab exposure, affecting CL, V(max), and V(1). The administration of concomitant chemotherapy (IFL, FOLFIRI, or paclitaxel/carboplatin) or intensity of baseline tumor EGFR expression did not alter the pharmacokinetics of panitumumab. The presence of antipanitumumab antibodies in patients (immunogenicity rate 3.4%) did not appear to affect panitumumab exposure substantially (AUC difference 8%). In support of a new drug application in Japan, the model was used to assess panitumumab pharmacokinetics in Japanese patients compared to other racial groups; there were no significant differences in model-predicted steady-state panitumumab AUC, C(max), or C(min) after accounting for the effect of body weight.
Hepatic expression of mature transforming growth factor beta 1 in transgenic mice results in multiple tissue lesions. (1995)

Aberrant expression of transforming growth factor beta 1 (TGF-beta 1) has been implicated in a number of disease processes, particularly those involving fibrotic and inflammatory lesions. To determine the in vivo effects of overexpression of TGF-beta 1 on the function and structure of hepatic as well as extrahepatic tissues, transgenic mice were generated containing a fusion gene (Alb/TGF-beta 1) consisting of modified porcine TGF-beta 1 cDNA under the control of the regulatory elements of the mouse albumin gene. Five transgenic lines were developed, all of which expressed the Alb/TGF-beta 1 transgene selectively in hepatocytes. The transgenic line 25 expressing the highest level of the transgene in the liver also had high (> 10-fold over control) plasma levels of TGF-beta 1. Hepatic fibrosis and apoptotic death of hepatocytes developed in all the transgenic lines but was more pronounced in line 25. The fibrotic process was characterized by deposition of collagen around individual hepatocytes and within the space of Disse in a radiating linear pattern. Several extrahepatic lesions developed in line 25, including glomerulonephritis and renal failure, arteritis and myocarditis, as well as atrophic changes in pancreas and testis. The results from this transgenic model strongly support the proposed etiological role for TGF-beta 1 in a variety of fibrotic and inflammatory disorders. The transgenic model may also provide an appropriate paradigm for testing therapeutic interventions aimed at neutralizing the detrimental effects of this important cytokine.
Floral Display and Pollination Success in Senecio jacobaea (Asteraceae): Interactive Effects of Head and Corymb Size (1996)

The self-sterile Senecio jacobaea (Asteraceae) presents its rayed heads in large, compound inflorescences (corymbs). I examined the role of head and corymb size in pollinator attraction, and whether the positive effect of intact rays (if any) depends on the size of the corymb. Using female fertility as a measure of pollination success, I assessed the performance of stems representing four experimentally produced character combinations: (1) few heads without rays, (2) many heads without rays, (3) few heads with rays, and (4) many heads with rays. The proportion of flowers setting fruit was higher for intact stems (treatments 2, 4) than for stems on which the majority of the heads had been removed (treatments 1, 3), suggesting selection for maximum inflorescence production. By contrast, experimental removal of all rays had a relatively weak negative effect on fruit set, with few-headed stems (treatment 1) experiencing a greater reduction than stems with many heads (treatment 2). These results suggest that clusters of heads produce a synergistic effect on pollinator attraction, allowing plants to maintain high visitation rates even if there are drastic reductions in the basic attraction units. Hence, the number of heads and the attractiveness of the individual heads interacted in their effect on pollination success. Fruit set per flower differed greatly between sites and was positively correlated with plant density.
Phase knowledge enables rational screens for protein crystallization (2006)

We show that knowledge of the phase behavior of a protein allows one to create a rational screen that increases the success rate of crystallizing challenging proteins. The strategy is based on using microfluidics to perform large numbers of protein solubility experiments across many different chemical conditions to identify reagents for crystallization experiments. Phase diagrams were generated for the identified reagents and used to design customized crystallization screens for every protein. This strategy was applied with a 75% success rate to the crystallization of 12 diverse proteins, most of which failed to crystallize when using traditional techniques. The overall diffraction success rate was 33%, about double what was achieved with conventional automation in large-scale protein structure consortia. The higher diffraction success rates are achieved by designing customized crystallization screens using the phase behavior information for each target. The identification of reagents based on an understanding of protein solubility and the use of phase diagrams in the design of individualized crystallization screens therefore promotes high crystallization rates and the production of diffraction-quality crystals.
Satellite-Mediated Protection of Tomato Against Cucumber Mosaic Virus: I. Greenhouse Experiments and Simulated Epidemic Conditions in the Field (1991)

Cucumber mosaic virus (CMV) strain S, with its naturally occurring satellite, can be used as a biological control agent to protect tomato (Lycopersicon esculentum UC82B) plants against disease induced by two severe CMV strains (D and 16). In greenhouse experiments, tomato plants were preinoculated or vaccinated with total RNA extracted from CMV-S and when challenge-inoculated after 3 wk with the severe strains, were protected against their effects. No synergistic effects were observed in mixed infections of CMV-S and a number of viruses commonly infecting tomato. Satellite-mediated protection was more protective and could be established sooner after vaccination than conventional cross-protection (.)
Antibodies against West Nile Virus Nonstructural Protein NS1 Prevent Lethal Infection through Fc γ Receptor-Dependent and -Independent Mechanisms (2006)

The flavivirus nonstructural protein NS1 is a highly conserved secreted glycoprotein that does not package with the virion. Immunization with NS1 elicits a protective immune response against yellow fever, dengue, and tick-borne encephalitis flaviviruses through poorly defined mechanisms. In this study, we purified a recombinant, secreted form of West Nile virus (WNV) NS1 glycoprotein from baculovirus-infected insect cells and generated 22 new NS1-specific monoclonal antibodies (MAbs). By performing competitive binding assays and expressing truncated NS1 proteins on the surface of yeast (Saccharomyces cerevisiae) and in bacteria, we mapped 21 of the newly generated MAbs to three NS1 fragments. Prophylaxis of C57BL/6 mice with any of four MAbs (10NS1, 14NS1, 16NS1, and 17NS1) strongly protected against lethal WNV infection (75 to 95% survival, respectively) compared to saline-treated controls (17% survival). In contrast, other anti-NS1 MAbs of the same isotype provided no significant protection. Notably, 14NS1 and 16NS1 also demonstrated marked efficacy as postexposure therapy, even when administered as a single dose 4 days after infection. Virologic analysis showed that 17NS1 protects at an early stage in infection through a C1q-independent and Fc gamma receptor-dependent pathway. Interestingly, 14NS1, which maps to a distinct region on NS1, protected through a C1q- and Fc gamma receptor-independent mechanism. Overall, our data suggest that distinct regions of NS1 can elicit protective humoral immunity against WNV through different mechanisms.
Targeting multiple types of tumors using NKG2D-coated iron oxide nanoparticles (2014)

Iron oxide nanoparticles (IONPs) hold great potential for cancer therapy. Actively targeting IONPs to tumor cells can further increase therapeutic efficacy and decrease off-target side effects. To target tumor cells, a natural killer (NK) cell activating receptor, NKG2D, was utilized to develop pan-tumor targeting IONPs. NKG2D ligands are expressed on many tumor types and its ligands are not found on most normal tissues under steady state conditions. The data showed that mouse and human fragment crystallizable (Fc)-fusion NKG2D (Fc-NKG2D) coated IONPs (NKG2D/NPs) can target multiple NKG2D ligand positive tumor types in vitro in a dose dependent manner by magnetic cell sorting. Tumor targeting effect was robust even under a very low tumor cell to normal cell ratio and targeting efficiency correlated with NKG2D ligand expression level on tumor cells. Furthermore, the magnetic separation platform utilized to test NKG2D/NP specificity has the potential to be developed into high throughput screening strategies to identify ideal fusion proteins or antibodies for targeting IONPs. In conclusion, NKG2D/NPs can be used to target multiple tumor types and magnetic separation platform can facilitate the proof-of-concept phase of tumor targeting IONP development.