gebhart/patrepeval huggingface dataset:
OPTIMIZING CULTURE CONDITIONS FOR THE PRODUCTION OF ANIMAL CELLS IN MICROCARRIER CULTURE (1981)

Cytodex 1 microcarriers have been used for the successful culture of more than 80 different types of animal cells--including primary cells, normal diploid cell strains and established or transformed cell lines. culture volumes have ranged from a few milliliters for diagnostic studies to over several hundred liters for vaccine production. Experience with this wide variety of cell types and culture volumes has enabled the identification of several parameters critical for obtaining maximum cell yields from microcarrier cultures. The most vital stage for the successful microcarrier culture of many cell types was the initial stage of the culture cycle. To achieve high cell yields, it was necessary to use culture procedures which maximized plating efficiency and final cell yield could be further increased by ensuring that the inoculation cell density exceeded a critical viable cell/microcarrier ratio. Modifications of the standard microcarrier culture procedures included reducing initial culture volume, reducing the initial stirring speed and/or supplementing the medium during the early stages of the culture cycle. Control of pH, nutrient supply, and gas tension were all critical throughout the culture cycle. Results with low-serum and serum-free media indicate that the requirement for fetal calf serum in the microcarrier culture of Vero and MRC-5 cells can be reduced or even eliminated. Large scale microcarrier culture equipment should take into account the modified culture procedures which are often required to achieve the full potential of this culture method. The design of a new flexible culture system suitable for pilot and production scale cultures is presented. This system accomodates a wide variety of culture and production procedures and through a recirculation system permits: (a) "in-line" monitoring and control of culture parameters; (b) provides an efficient gas exchange capacity which obviates the need for fermenter headspace and sparging; and (c) allows for maximal utilization of medium components and rapid harvesting of medium or cell products.
A Parallel Dose-Escalation Study of Weekly and Twice-Weekly Bortezomib in Combination with Gemcitabine and Cisplatin in the First-Line Treatment of Patients with Advanced Solid Tumors (2007)

Weekly bortezomib 1.0 mg/m(2) plus gemcitabine 1,000 mg/m(2) and cisplatin 70 mg/m(2) is the recommended phase 2 schedule, constituting a safe combination, with activity in NSCLC.
A major histocompatibility complex class I-related Fc receptor for IgG on rat hepatocytes. (1995)

Intestinal epithelial cells of the neonatal rat and mouse have been shown to express a major histocompatibility complex (MHC) class I-like Fc receptor, or FcRn, which transports IgG in an apical to basolateral direction. Previous studies have suggested the possible expression of this receptor beyond the neonatal period within the liver. Since bile contains high levels of IgG, we sought to determine whether the FcRn was functionally expressed by adult rat hepatocytes. Using primers specific for FcRn, which did not cross hybridize with MHC class I transcripts, FcRn DNA was amplified by reverse transcriptase polymerase chain reaction from RNA of adult rat hepatocytes. This RNA contained functional FcRn transcripts as it encoded a beta 2-microglobulin-associated cell surface protein as determined by immunoprecipitation of biotinylated cell surface proteins with a polyclonal anti-FcRn specific antiserum. Western blotting of hepatocyte canalicular (apical) and sinusoidal (basolateral) plasma membranes with an FcRn-specific monoclonal antibody further confirmed the protein expression and suggested that FcRn was enriched on the canalicular surface membranes. FcRn, on the surface of hepatocytes, was biologically functional as it bound Fc fragments of IgG at pH 6.0 but not 8.0, which is the same pH dependence observed for FcRn in rat neonatal enterocytes. Thus, FcRn is functionally expressed outside of the neonatal period on the canalicular cell surface of adult hepatocytes. This suggests that hepatocyte FcRn may bind luminal IgG, providing a potential functional communication between parenchymal immune cells and bile.
PACAP is Implicated in the Stress Axes (2011)

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a highly conserved pleiotropic neuropeptide that functions as a neurotransmitter, neuromodulator and neurotrophic factor. Accumulating evidence implicates PACAP as an important regulator of both central and/or peripheral components of the stress axes, particularly exposure to prolonged or traumatic stress. Indeed, PACAP and its cognate receptors are widely expressed in the brain regions and peripheral tissues that mediate stress-related responses. In the sympathoadrenomedullary system, PACAP is required for sustained epinephrine secretion during metabolic stress. It is likely that PACAP regulates autonomic function and contributes to peripheral homeostasis by maintaining a balance between sympathetic and parasympathetic activity, favoring stimulation of the sympathetic system. Furthermore, PACAP is thought to act centrally on the paraventricular nucleus of the hypothalamus to regulate both the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system. Intriguingly, PACAP is also active in brain structures that mediate anxiety- and fear-related behaviors, and the expression of PACAP and its receptors are dynamically altered under pathologic conditions. Thus PACAP may influence both hard-wired (genetically determined) stress responses and gene-environment interactions in stress-related psychopathology. This article aims to overview the molecular mechanisms and psychiatric implications of PACAP-dependent stress responses.
Characterization of a cyanobacterial photosystem I complex. (1985)

A simple procedure is described for the preparation of photosystem I (PSI) particles from Triton X-100-solubilized thylakoid membranes of the unicellular cyanobacterium Synechococcus 6301. The purified PSI complex contained the full complement of antenna chlorophylls, 130 +/- 5/P700, displayed the electron paramagnetic resonance signals characteristic of iron-sulfur centers X, A, and B, and had a protein/chlorophyll ratio of 2.9. Determination of the polypeptide composition, utilizing a uniformly 14C-labeled complex, showed that it contained polypeptides of 70, 18, 17.7, 16, and 10 kDa, in a molar ratio of 4.0:0.7:1.0:0.5:1.6. The relative amount of the lower molecular weight polypeptides showed progressive decrease with increase in Triton X-100 concentration and time of exposure to detergent. Consequently, it is proposed that in vivo the composition of the complex is [70 kDa]4 [18 kDa]1 [17.7 kDa]1 [16 kDa]1 [10 kDa]2. Relative to 130 mol of chlorophyll a, the PSI complex contained 16 mol of carotenoids, 13.7 +/- 1.0 g atoms of Fe, and 12.2 +/- 1.1 g atoms of labile sulfide. The properties of complexes fully depleted of the low-molecular weight polypeptides by treatment with sodium dodecyl sulfate or with proteinase K are also described.
Antimalarial dyes revisited: xanthenes, azines, oxazines, and thiazines (1995)

In 1891 Guttmann and Ehrlich (P. Guttmann and P. Ehrlich, Berlin Klin. Wochenschr. 28:953-956, 1891) were the first to report the antimalarial properties of a synthetic, rather than a natural, material when they described the clinical cure of two patients after oral administration of a thiazine dye, methylene blue. Since that time, sporadic reports of the antimalarial properties of several xanthene and azine dyes related to methylene blue have been noted. We report here the results from a reexamination of the antimalarial properties of methylene blue. Janus green B, and three rhodamine dyes and disclose new antimalarial data for 16 commercially available structural analogs of these dyes. The 50% inhibitory concentrations for the chloroquine-susceptible D6 clone and SN isolate and the chloroquine-resistant W2 clone of Plasmodium falciparum were determined by the recently described parasite lactate dehydrogenase enzyme assay. No cross-resistance to chloroquine was observed for any of the dyes. For the 21 dyes tested, no correlation was observed between antimalarial activity and cytotoxicity against KB cells. No correlation between log P (where P is the octanol/water partition coefficient) or relative catalyst efficiency for glucose oxidation and antimalarial activity or cytotoxicity was observed for the dyes as a whole or for the thiazine dyes. The thiazine dyes were the most uniformly potent structural class tested, and among the dyes in this class, methylene blue was notable for both its high antimalarial potency and selectivity.
Genetic Alterations of the Thrombopoietin/MPL/JAK2 Axis Impacting Megakaryopoiesis (2017)

Megakaryopoiesis is an original and complex cell process which leads to the formation of platelets. The homeostatic production of platelets is mainly regulated and controlled by thrombopoietin (TPO) and the TPO receptor (MPL)/JAK2 axis. Therefore, any hereditary or acquired abnormality affecting this signaling axis can result in thrombocytosis or thrombocytopenia. Thrombocytosis can be due to genetic alterations that affect either the intrinsic MPL signaling through gain-of-function (GOF) activity (<i>MPL, JAK2, CALR</i>) and loss-of-function (LOF) activity of negative regulators (<i>CBL, LNK</i>) or the extrinsic MPL signaling by <i>THPO</i> GOF mutations leading to increased TPO synthesis. Alternatively, thrombocytosis may paradoxically result from mutations of <i>MPL</i> leading to an abnormal MPL trafficking, inducing increased TPO levels by alteration of its clearance. In contrast, thrombocytopenia can also result from LOF <i>THPO</i> or <i>MPL</i> mutations, which cause a complete defect in MPL trafficking to the cell membrane, impaired MPL signaling or stability, defects in the TPO/MPL interaction, or an absence of TPO production.
Standardized Quantification of Pulmonary Fibrosis in Histological Samples (2008)

The Ashcroft scale for the evaluation of bleomycin-induced lung fibrosis is the analysis of stained histological samples by visual assessment. Based on the knowledge that this procedure is not standardized in animals and results are highly variable, we hypothesized that modification of this method may improve quantification of lung fibrosis in small animals. To prove our hypothesis, we evaluated pulmonary fibrosis in Lewis rats induced by a single intratracheal injection of 0.3 mg/kg body weight bleomycin (n = 13) compared with the same amount of saline in a control group (n = 4). We modified the Ashcroft scale by precisely defining the assignment of grades from 0 to 8 for the increasing extent of fibrosis in lung histological samples. Thirty-two observers were randomly assigned to evaluate 108 photographs of slides using either the Ashcroft scale or the modified scale. Consistent with our hypothesis, there was a significant reduction in the variability of standard deviations with the modified scale compared with the Ashcroft scale (mean of variability 0.25 versus 0.62, P < 0.0001). Applying the kappa index, the Ashcroft scale showed only a fair to moderate agreement (0.23-0.59) between the observers and a low intra-observer agreement (0.51-0.74) in contrast to the modified scale, which demonstrated a moderate to good agreement between the observers (0.65-0.93, P < 0.0001) and a high intra-observer agreement (0.87-0.91, P < 0.05). To test the modified scale in vivo, we compared both scales with the results of computed tomography (CT) of the lungs obtained from the same mice. In agreement, the modified scale demonstrated a better correlation to CT scans (R = 0.58) compared with the Ashcroft scale (R = 0.33). In summary, quantification of lung fibrosis in histological lung sections using the modified scale is reliable and reproducible.
Functional role of human immunodeficiency virus type 1 vpu. (1989)

To investigate the role of vpu in the replication and cytopathicity of human immunodeficiency virus type 1 (HIV-1), infectious proviruses were constructed that were isogenic except for the ability to produce the protein product of vpu. The vpu-encoded protein is shown to decrease the rate of syncytium formation and cell killing in infected CD4+ human T cells, to increase greatly the export of virus particles from infected cells, and to reduce the rate of accumulation of cell-associated viral proteins. The vpu protein complements in trans the defect in a vpu- HIV-1 provirus but does not affect the simian immunodeficiency virus, which lacks vpu. These observations suggest that vpu may contribute to the AIDS epidemic by increasing the transmission efficiency of the virus.
Involvement of integrins alpha v beta 3 and alpha v beta 5 in ocular neovascular diseases. (1996)

Angiogenesis underlies the majority of eye diseases that result in catastrophic loss of vision. Recent evidence has implicated the integrins alpha v beta 3 and alpha v beta 5 in the angiogenic process. We examined the expression of alpha v beta 3 and alpha v beta 5 in neovascular ocular tissue from patients with subretinal neovascularization from age-related macular degeneration or the presumed ocular histoplasmosis syndrome or retinal neovascularization from proliferative diabetic retinopathy (PDR). Only alpha v beta 3 was observed on blood vessels in ocular tissues with active neovascularization from patients with age-related macular degeneration or presumed ocular histoplasmosis, whereas both alpha v beta 3 and alpha v beta 5 were present on vascular cells in tissues from patients with PDR. Since we observed both integrins on vascular cells from tissues of patients with retinal neovascularization from PDR, we examined the effects of a systemically administered cyclic peptide antagonist of alpha v beta 3 and alpha v beta 5 on retinal angiogenesis in a murine model. This antagonist specifically blocked new blood vessel formation with no effect on established vessels. These results not only reinforce the concept that retinal and subretinal neovascular diseases are distinct pathological processes, but that antagonists of alpha v beta 3 and/or alpha v beta 5 may be effective in treating individuals with blinding eye disease associated with angiogenesis.
Transglycation—A Potential New Mechanism for Deglycation of Schiff's Bases (2005)

Nonenzymatic glycation is believed to play a major role in the development of diabetic complications. Over the past several years we and others have shown that in cells this nonenzymatic process can be reversed by an ATP-dependent reaction catalyzed by fructosamine-3-kinase (FN3K) and possibly by its isozyme, fructosamine-3-kinase-related protein (FN3KRP). In this study we provide the first evidence that this FN3K-dependent deglycation, acting on the Amadori products, is complemented by another deglycation process operating on the very first product of nonenzymatic glycation, glucosylamines (Schiff's bases). We postulate that the first step in this Schiff's-base deglycation process occurs by transfer of the sugar moiety from macromolecule-bound glucosylamine to one of the low-molecular weight intracellular nucleophiles-in particular, glutathione. We term this reaction transglycation, and in this study we demonstrate that it occurs readily and spontaneously in vitro. We further propose that one of the spontaneously formed glucose-glutathione adduct(s) is subsequently removed from cells by a multidrug-resistance pump (MRP, MDR-protein, ATP-binding-cassette protein), metabolized, and excreted in urine. In support of this latter contention, we show that at least one transglycation product, glucose-cysteine, is found in human urine and that its concentrations are increased in diabetes.
Optimal Decentralized Load Frequency Control (1987)

The paper presents a novel methodology for feasibility analysis and design of optimal decentralized load frequency control for multi-area interconnected electric power systems. Feasibility of the proposed decentralized control scheme is determined with a fixed mode evaluation algorithm based on eigenvalue dynamics. The eigenvalue sensitivity expressions are also used to determine decentralized feedback gains that will result in system transient performance similar to the one obtained with a centralized optimal control law. The methodology is illustrated with a two-area power system example.
Prenylation of olivetolate by a hemp transferase yields cannabigerolic acid, the precursor of tetrahydrocannabinol (1998)

A new enzyme, geranylpyrophosphate:olivetolate geranyltransferase (GOT), the first enzyme in the biosynthesis of cannabinoids could be detected in extracts of young leaves of Cannabis sativa. The enzyme accepts geranylpyrophosphate (GPP) and to a lesser degree also nerylpyrophosphate (NPP) as a cosubstrate. It is, however, specific for olivetolic acid; its decarboxylation product olivetol is inactive as a prenyl acceptor.
Guarded execution and branch prediction in dynamic ILP processors (1994)

We evaluate the effects of guarded (or conditional, or predicated) execution on the performance of an instruction level parallel processor employing dynamic branch prediction. First, we assess the utility of guarded execution, both qualitatively and quantitatively, using a variety of application programs. Our assessment shows that guarded execution significantly increases the opportunities, for both compiler and dynamic hardware, to extract and exploit parallelism. However, existing methods of specifying guarded execution have several drawbacks that limit its use. Second, we study the interaction of guarded execution and dynamic branch prediction and show that the use of guarded execution significantly increases the number of instructions between mispredicted branches. Third, we propose a new method of specifying guarded execution. The proposed method uses special GUARD instructions, which can be used to incorporate guarded execution into existing instruction sets. GUARD instructions realize the full power of guarded execution, without the drawbacks of existing methods of specifying guarded execution.
Silicide formation in Pd-a-Si:H Schottky barriers (1981)

This letter gives the first report of a direct correlation of Schottky barrier characteristics to silicide growth on a-Si:H. Changes in diode ideality factor (from 1.2 to 1.05) produced by annealing can now be directly attributed to growth of Pd2Si as demonstrated by Raman spectroscopy. Unannealed samples show long-term changes in characteristics at room temperature due to slow silicide growth. However, Pd Schottky barriers possess ideal stable characteristics once silicide growth is complete.
What Genetics Tells us About the Causes and Mechanisms of Parkinson's Disease (2011)

Parkinson's disease (PD) is a common motor disorder of mysterious etiology. It is due to the progressive degeneration of the dopaminergic neurons of the substantia nigra and is accompanied by the appearance of intraneuronal inclusions enriched in α-synuclein, the Lewy bodies. It is becoming increasingly clear that genetic factors contribute to its complex pathogenesis. Over the past decade, the genetic basis of rare PD forms with Mendelian inheritance, representing no more than 10% of the cases, has been investigated. More than 16 loci and 11 associated genes have been identified so far; genome-wide association studies have provided convincing evidence that polymorphic variants in these genes contribute to sporadic PD. The knowledge acquired of the functions of their protein products has revealed pathways of neurodegeneration that may be shared between inherited and sporadic PD. An impressive set of data in different model systems strongly suggest that mitochondrial dysfunction plays a central role in clinically similar, early-onset autosomal recessive PD forms caused by parkin and PINK1, and possibly DJ-1 gene mutations. In contrast, α-synuclein accumulation in Lewy bodies defines a spectrum of disorders ranging from typical late-onset PD to PD dementia and including sporadic and autosomal dominant PD forms due to mutations in SCNA and LRRK2. However, the pathological role of Lewy bodies remains uncertain, as they may or may not be present in PD forms with one and the same LRRK2 mutation. Impairment of autophagy-based protein/organelle degradation pathways is emerging as a possible unifying but still fragile pathogenic scenario in PD. Strengthening these discoveries and finding other convergence points by identifying new genes responsible for Mendelian forms of PD and exploring their functions and relationships are the main challenges of the next decade. It is also the way to follow to open new promising avenues of neuroprotective treatment for this devastating disorder.
Development of a Multiple Marker Test for Ectopic Pregnancy (2011)

: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00194168.
Enabling a microfluidic immunoassay for the developing world by integration of on-card dry reagent storage (2008)

As part of an effort to create a point-of-care diagnostic system for the developing world, we present a microfluidic flow-through membrane immunoassay with on-card dry reagent storage. By preserving reagent function, the storage and reconstitution of anhydrous reagents enables the devices to remain viable in challenging, unregulated environmental conditions. The assay takes place on a disposable laminate card containing both a porous membrane patterned with capture molecules and a fibrous pad containing an anhydrous analyte label. To conduct the assay, the card is placed in an external pumping and imaging instrument capable of delivering sample and rehydrated reagent to the assay membrane at controlled flow rates to generate quantitative results. Using the malarial antigen Plasmodium falciparum histidine-rich protein II (PfHRP2) as a model, we demonstrate selection of dry storage conditions, characterization of reagent rehydration, and execution of an automated on-card assay. Gold-antibody conjugates dried in a variety of sugar matrices were shown to retain 80-96% of their activity after 60 days of storage at elevated temperatures, and the release profile of the reconstituted reagent was characterized under flow in microfluidic channels. The system gave a detection limit in the sub-nanomolar range in under nine minutes, showing the potential to expand into quantitative, multi-analyte analysis of human blood samples.
Fast calculation of soft shadow textures using convolution (1998)

The calculation of detailed shadows remains one of the most difficult challenges in computer graphics, especially in the case of extended (linear or area) light sources. This paper introduces a new tool for the calculation of shadows cast by extended light sources. Exact shadows are computed in some constrained configurations by using a convolution technique, yielding a fast and accurate solution. Approximate shadows can be computed for general configurations by applying the convolution to a representative "ideal" configuration. We analyze the various sources of approximation in the process and derive a hierarchical, error-driven algorithm for fast shadow calculation in arbitrary configurations using a hierarchy of object clusters. The convolution is performed on images rendered in an offscreen buffer and produces a shadow map used as a texture to modulate the unoccluded illumination. Light sources can have any 3D shape as well as arbitrary emission characteristics, while shadow maps can be applied to groups of objects at once. The method can be employed in a hierarchical radiosity system, or directly as a shadowing technique. We demonstrate results for various scenes, showing that soft shadows can be generated at interactive rates for dynamic environments.