gebhart/patrepeval huggingface dataset:
Cytoskeletal dissolution blocks oxidant release and cell death in injured cartilage (2011)

The mechanisms by which articular surface impact causes post-traumatic osteoarthritis are not well understood, but studies of cartilage explants implicate the mitochondrial electron transport chain as a source of oxidants that cause chondrocyte death from mechanical injury. The linkage of mitochondria to the cytoskeleton suggests that they might release oxidants in response to mechanical strain, an effect that disrupting the cytoskeleton would prevent. To test this we investigated the effects of agents that promote the dissolution of microfilaments (cytochalasin B) or microtubules (nocodazole) on oxidant production and chondrocyte death following impact injury. Osteochondral explants treated with cytochalasin B or nocodazole for 4 h were impacted (7 J/cm(2)) and stained for oxidant production directly after impact and for cell viability 24 h after impact. Surfaces within and outside impact sites were then imaged by confocal microscopy. Both agents significantly reduced impact-induced oxidant release (p < 0.05); however, cytochalasin B was more effective than nocodazole (>60% reduction vs. 40% reduction, respectively). Both agents also prevented impact induced cell death. Dissolution of the cytoskeleton by both drugs was confirmed by phalloidin staining and confocal microscopy. These findings show that chondrocyte mortality from impact injury depends substantially on mitochondrial-cytoskeletal linkage, suggesting new approaches to stem mechanically induced cartilage degeneration.
Removal of Visceral Fat Prevents Insulin Resistance and Glucose Intolerance of Aging (2002)

Age-dependent changes in insulin action and body fat distribution are risk factors for the development of type 2 diabetes. To examine whether the accumulation of visceral fat (VF) could play a direct role in the pathophysiology of insulin resistance and type 2 diabetes, we monitored insulin action, glucose tolerance, and the expression of adipo-derived peptides after surgical removal of VF in aging (20-month-old) F344/Brown Norway (FBN) and in Zucker Diabetic Fatty (ZDF) rats. As expected, peripheral and hepatic insulin action were markedly impaired in aging FBN rats, and extraction of VF (accounting for approximately 18% of their total body fat) was sufficient to restore peripheral and hepatic insulin action to the levels of young rats. When examined at the mechanistic level, removal of VF in ZDF rats prevented the progressive decrease in insulin action and delayed the onset of diabetes, but VF extraction did not alter plasma free fatty acid levels. However, the expression of tumor necrosis factor-alpha and leptin in subcutaneous (SC) adipose tissue were markedly decreased after VF removal (by approximately three- and twofold, respectively). Finally, extracted VF retained approximately 15-fold higher resistin mRNA compared with SC fat. Our data suggest that insulin resistance and the development of diabetes can be significantly reduced in aging rats by preventing the age-dependent accumulation of VF. This study documents a cause-and-effect relationship between VF and major components of the metabolic syndrome.
Adaptive Compression and Joint Detection for Fronthaul Uplinks in Cloud Radio Access Networks (2015)

Cloud radio access network (C-RAN) has recently attracted much attention as a promising architecture for future mobile networks to sustain the exponential growth of data rate. In C-RAN, one data processing center or baseband unit (BBU) communicates with users via distributed remote radio heads (RRHs), which are connected to the BBU via high capacity, low latency fronthaul links. In this paper, we study the compression on fronthaul uplinks and propose a joint decompression algorithm at the BBU. The central premise behind the proposed algorithm is to exploit the correlation between RRHs. Our contribution is threefold. First, we propose a joint decompression and detection (JDD) algorithm which jointly performs decompressing and detecting. The JDD algorithm takes into consideration both the fading and compression effect in a single decoding step. Second, block error rate (BLER) of the proposed algorithm is analyzed in closed-form by using pair-wise error probability analysis. Third, based on the analyzed BLER, we propose adaptive compression schemes subject to quality of service (QoS) constraints to minimize the fronthaul transmission rate while satisfying the pre-defined target QoS. As a dual problem, we also propose a scheme to minimize the signal distortion subject to fronthaul rate constraint. Numerical results demonstrate that the proposed adaptive compression schemes can achieve a compression ratio of 300% in experimental setups.
Spray-Drying of Food Flavors (1988)

Spray drying is the most commonly used technique for the production of dry flavorings. In spray drying, an aqueous infeed material (water, carrier, and flavor) is atomized into a stream of hot air. The atomized particles dry very rapidly, trapping volatile flavor constituents inside the droplets. The powder is recovered via cyclone collectors. Flavor retention is quite satisfactory if dryer operating parameters are properly chosen. Flavor retention is maximized by using a high infeed solids level, high viscosity infeed, optimum inlet (160-210 C) and high exit (>100 C) air temperatures and high molecular weight flavor molecules. The shelf-life of oxidizable flavor compounds is strongly influenced by the flavor carrier.
Ammonium Chloride-Promoted Four-Component Synthesis of Pyrrolo[3,4-b]pyridin-5-one (2002)

A novel multicomponent synthesis of 5-aminooxazole starting from simple and readily available inputs is described. Thus, simply heating a methanol solution of an aldehyde 3, an amine 4, and an alpha-isocyanoacetamide 5 provided the 5-aminooxazole (1) in good to excellent yield. The reaction of 1 with alpha,beta-unsaturated acyl chloride 13 lead to the formation of pyrrolo[3,4-b]pyridin-5-one (2) in a single operation. A triple domino sequence, acylation/IMDA/retro-Michael cycloreversion, is involved in this new scaffold-generating reaction. After the observation that ammonium chloride can significantly accelerate the oxazole formation in toluene, a one-pot four-component synthesis of 2 is developed.
Rising CO2 levels and their potential significance for carbon flow in photosynthetic cells (1991)

Abstract. In the first part of this review, I discuss how we can predict the direct short‐term effect of enhanced CO 2 on photosynthetic rate in C 3 terrestrial plants. To do this, I consider: (1) to what extent enhanced CO 2 will stimulate or relieve demand on partial processes like carboxylation, light harvesting and electron transport, the Calvin cycle, and end‐product synthesis; and (2) the extent to which these various processes actually control the rate of photosynthesis. I conclude that control is usually shared between Rubisco (which responds sensitively to CO 2 ) and other components (which respond less sensitively), and that photosynthesis will be stimulated by 25–75% when the CO 2 concentration is doubled from 35 to 70 Pa. This is in good agreement with the published responses. In the next part of the review, I discuss the evidence that most plants undergo a gradual inhibition of photosynthesis during acclimation to enhanced CO 2 . I argue that this is related to an inadequate demand for carbohydrate in the remainder of the plant. Differences in the long‐term response to CO 2 may be explained by differences in the sink‐source status of plants, depending upon the species, the developmental stage, and the developmental conditions. In the third part of the review, I consider the biochemical mechanisms which are involved in ‘sink’ regulation of photosynthesis. Accumulating carbohydrate could lead to a direct inhibition of photosynthesis, involving mechanical damage by large starch grains or Pi‐limitation due to inhibition of sucrose synthesis. I argue that Pi is important in the short‐term regulation of partitioning to sucrose and starch, but that its contribution to ‘sink’ regulation has not yet been conclusively demonstrated. Indirect or ‘adaptive’ regulation of photosynthesis is probably more important, involving decreases in amounts of key photosynthetic enzymes, including Rubisco. This decreases the rate of photosynthesis, and potentially would allow resources (e.g. amino acids) to be remobilized from the leaves and reinvested in sink growth to readjust the sink‐source balance. In the final part of the review, I argue that similar changes of Rubisco and, possibly, other proteins are probably also involved during acclimation to high CO 2 .
PD-1 and PD-1 ligands: from discovery to clinical application (2007)

Programmed cell death-1 (PD-1, Pdcd1), an immunoreceptor belonging to the CD28/CTLA-4 family negatively regulates antigen receptor signaling by recruiting protein tyrosine phosphatase, SHP-2 upon interacting with either of two ligands, PD-L1 or PD-L2. Because of the wide range of ligand distribution in the body, its biological significance pervades almost every aspect of immune responses including autoimmunity, tumor immunity, infectious immunity, transplantation immunity, allergy and immunological privilege. In this review, we would like to summarize the history of PD-1 research since its discovery and recent findings that suggest promising future for the clinical application of PD-1 agonists and antagonists to various human diseases.
Prolonged activation of the mitogen-activated protein kinase pathway is required for macrophage-like differentiation of a human myeloid leukemic cell line. (2000)

The role of the mitogen-activated protein kinase (MAPK) signal transduction pathway in the proliferation of mammalian cells has been well established. However, there are relatively few reports concerning cell differentiation being mediated by MAPK. The effect of phorbol 12-myristate 13-acetate (PMA) on cell differentiation and signal transduction in a human myeloid leukemia cell line, TF-1a, was investigated. When TF-1a cells were treated with 10(-6), 10(-7), 10(-8), and 10(-9) M PMA for 24 h, they underwent 98, 93, 91, and 51% macrophage-like differentiation, respectively. PMA treatment rapidly (10 min) induced phosphorylation of MAPK kinase (MEK and p44/42 MAPK), which persisted for at least 24 h. p44/42 MAPK immunoprecipitates from lysates of PMA-treated cells had increased ability to phosphorylate the transcription factor Elk-1. This is important because phosphorylated Elk-1 can be considered an "end-product" of the MAPK pathway. In contrast, treatment of TF-1a cells with granulocyte/macrophage-colony stimulating factor induced only transient activation of MEK and p44/42 MAPK (10-20 min) and an increase (approximately 50%) in cell proliferation, without any change in cellular differentiation. These results suggest that macrophage-like differentiation may be dependent on prolonged activation of the MAPK pathway. Additional support for this conclusion was obtained from experiments showing that treatment of TF-1a cells with antisense oligonucleotides for MEK1 coding sequences prior to adding PMA inhibited macrophage-like differentiation. Furthermore, transient transfection with an inactive, dominant-negative MEK mutant also inhibited PMA-induced differentiation, whereas transient transfection with a plasmid coding for constitutively activated MEK led to macrophage-like differentiation in the absence of PMA.
Design of a Potential Colonic Drug Delivery System of Mesalamine (2008)

The aim of the present investigation was to develop a site-specific colonic drug delivery system, built on the principles of the combination of pH and time sensitivity. Press-coated mesalamine tablets with a coat of HPMC E-15 were over-coated with Eudragit S100. The in vitro drug release study was conducted using sequential dissolution technique at pH 1.2, 6.0, 7.2 and 6.4 mimicking different regions of gastrointestinal tract. The optimized batch (F2) showed less than 6% of drug release before reaching colonic pH 6.4 and complete drug release was obtained thereafter within 2 hr. A short-term dissolution stability study demonstrated statistical insignificant difference in drug release.
Performance Enhancements of Viscoelastic Surfactant Stimulation Fluids with Nanoparticles (2008)

Abstract High-molecular-weight crosslinked polymer fluids have been used to stimulate oil and gas wells for decades. These fluids exhibit exceptional viscosity, thermal stability, proppant transportability, and fluid leak-off control. However, a major drawback of crosslinked polymer fluids is the amount of polymer residue they leave behind. Polymer residue has been shown to significantly damage formation permeability and fracture conductivity. 1-3 Recently, viscoelastic surfactant (VES) fluids composed of low-molecular-weight surfactants have been used as hydraulic fracturing and frac-packing fluids. The surfactants structurally arrange in brine to form rod-like micelles that exhibit viscoelastic fluid behavior. VES fluids, once broken, leave very little residue or production damage. However, excessive fluid leak-off and poor thermal stability has significantly limited their use. This paper will introduce newly developed, select nano-size crystals with unique surface charges and will explain how nanoparticle technology pseudo-crosslinks VES rod-like micelles together to improve the fluid loss control and proppant transport of VES fluids to a performance level similar to that of crosslinked polymer fluid. The nanoparticle pseudo-crosslinked VES micelle fluid develops a wall-building pseudo-filtercake on the face of porous media to control fluid loss. When internal breakers are used to degrade the VES micelle structures the leaked-off VES fluid and the pseudo-filtercake breaks into brine water and nanoparticles. Since the nanoparticles are very small and readily pass through the pores of greater than 0.1 md formations, they are flowed back with the produced fluids, and no internal or external "solids" damage is generated. This paper will present laboratory data that shows how uniquely charged nanoparticles improve VES fluid rheology, leak-off control, and proppant suspension. Also presented are test results comparing nanoparticle enhanced VES to borate crosslinked guar polymer fluids. The mechanisms that enhance the performance of these fluids also will be discussed.
Complex Regulation of Signal Transducers and Activators of Transcription 3 Activation in Normal and Malignant Keratinocytes (2004)

Previous work implicated activation of the signal transducer and activator of transcription (STAT)3 downstream of the epidermal growth factor receptor (EGFR) in the malignant phenotype of squamous carcinoma cells (SCC). Here, we show that EGFR-dependent STAT3 activation is restricted to malignant keratinocytes. Specifically, constitutive and epidermal growth factor-induced phosphorylation of STAT3 on Y705 was observed only in SCC but not in either immortalized (HaCaT) or normal keratinocyte strains. Furthermore, STAT3 activation as determined by DNA binding assays was restricted to SCC and dependent on EGFR activation. Forced expression of EGFR in immortalized keratinocytes (HaCaT cells) was associated with enhanced EGFR activation but not STAT3-Y705 phosphorylation. EGFR-dependent activation of mitogen-activated protein kinase (MAPK) kinase 1 negatively regulated STAT3-Y705 phosphorylation in normal and malignant keratinocytes. Together, these results underscore that EGFR activation is required but not sufficient for STAT3 activation to occur in malignant keratinocytes. They also highlight complex regulation of STAT3 phosphorylation through EGFR activation including negative regulation via the MAPK kinase/MAPK signaling pathway.
Quantitative Study of the Effects of Surface Ligand Concentration on CdSe Nanocrystal Photoluminescence (2007)

We study the impact of surface chemistry on the photoluminescence (PL) quantum yield of CdSe core, CdSe/CdS core/shell, and CdSe/CdZnS/ZnS core/shell/shell nanocrystals prepared by multiple synthetic routes. We expose as-synthesized particles to varying concentrations of n-alkylamine and n-alkanethiol ligands and verify that the addition of n-alkanethiols to CdSe and CdSe/CdS nanocrystal solutions quenches their PL. We also show that the addition of n-alkylamines to nanocrystal solutions can increase or decrease nanocrystal PL, an effect that depends on the concentration of both nanocrystals and ligands. We demonstrate the importance of considering the nanocrystal concentration when fitting ligand binding curves, and show that common solvent impurities can affect the PL and ligand binding data. While alkanethiols quench CdSe nanocrystals prepared using multiple synthetic procedures, we find the exact shape of the quenching curve depends on the synthetic route chosen. We emphasize that the ligand binding data extracted from PL quenching curves are contingent on the assumptions made during fitting. By fitting our PL quenching curves to a Langmuir isotherm and accounting for the particle surface sites, we estimate a lower limit for the equilibrium CdSe−alkanethiol binding constant on the order of 109 M-1 with different numbers of thiol binding sites depending on the method of nanocrystal synthesis.
Dramatic Rise in Plasma Viremia after CD8+ T Cell Depletion in Simian Immunodeficiency Virus–infected Macaques (1999)

To determine the role of CD8(+) T cells in controlling simian immunodeficiency virus (SIV) replication in vivo, we examined the effect of depleting this cell population using an anti-CD8 monoclonal antibody, OKT8F. There was on average a 99.9% reduction of CD8 cells in peripheral blood in six infected Macaca mulatta treated with OKT8F. The apparent CD8 depletion started 1 h after antibody administration, and low CD8 levels were maintained until day 8. An increase in plasma viremia of one to three orders of magnitude was observed in five of the six macaques. The injection of a control antibody to an infected macaque did not induce a sustained viral load increase, nor did it significantly reduce the number of CD8(+) T cells. These results demonstrate that CD8 cells play a crucial role in suppressing SIV replication in vivo.
Structural Interlock between Ligand-Binding Site and Stalk-Like Region of 1 Integrin Revealed by a Monoclonal Antibody Recognizing Conformation-Dependent Epitope (1997)

Integrin activation and sebsequent ligand binding to it are regulated by intracellular mechanisms called inside-out signaling, which are not fully understood and are accompanied by dynamic structural changes of the integrin molecule itself. A monoclonal antibody recognizing a conformation-dependent epitope on human beta1 integrin was produced and characterized in detail. This antibody, AG89, reacted with human integrin beta1 chain regardless of the alpha subunit. AG89 can recognize resting state beta1 integrin on the cells, but the reactivity is increased approximately 2-fold upon integrin activation by activating anti-beta1 antibodies and approximately 3-fold by Mn2+. Furthermore, occupation of the ligand-binding pocket by a soluble ligand (RGD peptide for alpha(v)beta1 and CS-1 peptide for alpha4beta1) resulted in maximum binding of AG89, indicating that the epitope for AG89 is exposed during the conformational changes of beta1 integrin upon activation/ligation. Epitope mapping by using interspecies chimeric beta1 revealed that the epitope for AG89 lies within residues 426-587, which corresponds to the cysteine-rich repeat structure located in the middle of the beta1 chain. The fact that binding of AG89 itself could activate the resting beta1 integrin indicates that exposure of the AG89 epitope in the membrane-proximal stalk-like domain and "opening" of the ligand-binding pocket at the outermost domain are physically linked. We propose that the integrin "signaling" is mediated by this direct physical transduction of conformational information along the integrin molecule.
Design and Construction of Portable CRISPR-Cpf1-Mediated Genome Editing in Bacillus subtilis 168 Oriented Toward Multiple Utilities (2020)

<i>Bacillus subtilis</i> is an important Gram-positive bacterium for industrial biotechnology, which has been widely used to produce diverse high-value added chemicals and industrially and pharmaceutically relevant proteins. Robust and versatile toolkits for genome editing in <i>B. subtilis</i> are highly demanding to design higher version chassis. Although the <i>Streptococcus pyogenes</i> (<i>Sp</i>) CRISPR-Cas9 has been extensively adapted for genome engineering of multiple bacteria, it has many defects, such as higher molecular weight which leads to higher carrier load, low deletion efficiency and complexity of sgRNA construction for multiplex genome editing. Here, we designed a CRISPR-Cpf1-based toolkit employing a type V Cas protein, Cpf1 from <i>Francisella novicida.</i> Using this platform, we precisely deleted single gene and gene cluster in <i>B. subtilis</i> with high editing efficiency, such as <i>sacA</i>, <i>ganA, ligD</i> & <i>ligV</i>, and <i>bac</i> operon. Especially, an extremely large gene cluster of 38 kb in <i>B. subtilis</i> genome was accurately deleted from the genome without introducing any unexpected mutations. Meanwhile, the synthetic platform was further upgraded to a version for multiplex genome editing, upon which two genes <i>sacA</i> and <i>aprE</i> were precisely and efficiently deleted using only one plasmid harboring two targeting sequences. In addition, we successfully inserted foreign genes into the genome of the chassis using the CRISPR-Cpf1 platform. Our work highlighted the availability of CRISPR-Cpf1 to gene manipulation in <i>B. subtilis</i>, including the flexible deletion of a single gene and multiple genes or a gene cluster, and gene knock-in. The designed genome-editing platform was easily and broadly applicable to other microorganisms. The novel platforms we constructed in this study provide a promising tool for efficient genome editing in diverse bacteria.
Detection of Aspergillus Galactomannan: Comparison of an Enzyme-Linked Immunoassay and a Europium-Linked Time-Resolved Fluoroimmunoassay (1998)

With a view to improving the sensitivity of serological detection of Aspergillus galactomannan (GM), a europium-linked time-resolved fluoroimmunoassay was developed. This method was compared to an enzyme-linked immunosorbent assay using a peroxidase-conjugated detector antibody. No increase in the sensitivity of the detection of GM standards was seen with the europium-based fluoroimmunoassay.
Restriction Fragment Length Polymorphism Linkage Map of Arabidopsis thaliana (1989)

Hong-Gil Nam, , Bart den Boer, Francis Moonan, William D. B. Loos, Brian M. Hauge, Howard M. Goodman, Restriction Fragment Length Polymorphism Linkage Map of Arabidopsis thaliana, The Plant Cell, Vol. 1, No. 7 (Jul., 1989), pp. 699-705