gebhart/patrepeval huggingface dataset:
Mouse Osteoblastic Cells (MC3T3-E1) at Different Stages of Differentiation Have Opposite Effects on Osteoclastic Cell Formation (1991)

Using our new culture system for multinucleate cells (MNCs) that have many characteristics of osteoclasts, we examined the effects of factors produced by osteoblastic cells on osteoclastic cell formation. Conditioned medium (CM) from undifferentiated osteoblastic MC3T3-E1 cells during their growth phase inhibited MNC formation in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) and 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3]. Diluted CM (1:81) from differentiated cells obtained after cultivation for more than 20 days stimulated MNC formation, but at lower dilutions inhibited their formation. Dialyzed CM (greater than 2000 mol wt) from the differentiated cells was more stimulatory than undialyzed CM and showed no inhibitory effect on MNC formation. The inhibitory effect was observed with filtered (less than 3000 mol wt) CMs and was specific for osteoblastic cell CM. Prostaglandin E2 (PGE2) was detected in the CM from undifferentiated or differentiated MC3T3-E1 cells at concentrations (317 +/- 66 and 1287 +/- 179 pg/ml, respectively) sufficient to inhibit MNC formation, and this inhibition was partially abolished with CM (at 3-fold dilution) in indomethacin-treated cells (PGE2, less than 20 pg/ml), suggesting PGE2-mediated inhibition of MNC formation and the presence of another factor(s) besides PGE2 that influenced MNC formation. In contrast to day 3 CM plus 1,25-(OH)2D3, day 60 CM plus 1,25-(OH)2D3 induced MNC formation even in the absence of GM-CSF, and this induction was inhibited by an antibody to GM-CSF. Secondary colony formation assays showed the presence of a GM-CSF-like factor in the day 60 CM. These findings indicate that osteoblastic cells are involved in the process of osteoclastic cell formation, with at least two soluble factors produced by osteoblasts, a GM-CSF-like factor, which is stimulatory, and PGE2, which is inhibitory. The effects of CMs also differed depending on the stage of osteoblast differentiation.
Field-assisted bonding below 200 °C using metal and glass thin-film interlayers (1987)

Bonding between similar or dissimilar surfaces with metal and glass thin-film interlayers as well as bulk glass plates using an electric field assisted bonding technique at 160 °C or less is described. This low-temperature field-assisted bonding is achieved using, e.g., few μm thick glass films rf magnetron sputter deposited from Na or Li silicate glasses, and 0.05–1.0 μm thick Al, Sn, Mg, and Hf films. The bond strength thus achieved is found to be greater than the cohesive strength of the glass used. Results from x-ray photoelectron spectroscopy analyses confirm the migration across the glass layer and the plating out on the cathode surfaces of mobile ions such as Na+ or Li+ during field-assisted bonding. The migration and plating out of mobile ions can be detected in 10 s after the potential is applied and whether actual bonding between the metal and glass occurs or not. The possible bonding mechanism based on these XPS results is proposed.
A new cache directory scheme (2002)

This paper proposes a new directory scheme with a balanced binary-tree structure that dynamically changes with current data sharing. It is scalable in allowing an unlimited number of caches to share the same data block, and can carry out coherence operations quickly, i.e., in logarithmic time. This scheme is especially appropriate for update-oriented coherence protocols where the sharing structure is preserved across writes. We demonstrate how the tree directories handle cache addition (a cache acquiring a data block copy) and cache deletion (a cache surrendering a data block copy due to its local block replacement), and present their respective time complexities. It can be shown that this kind of tree structure is an asymptotically optimal directory scheme for scalable architectures, carrying out all cache operations in minimum possible time.
DNA and RNA Sequence Determination Based on Phosphorothioate Chemistry (1988)

The difference in reactivity between phosphate and phosphorothioate diesters is the basis of a chemical degradation scheme for the sequencing of DNA and RNA. The phosphorothioate groups are incorporated into the nucleic acid in four separate enzymatic reactions, with three of the natural nucleoside triphosphates and one alpha-thiotriphosphate in each reaction. Selective strand cleavage is achieved through alkylation to form the hydrolytically labile phosphorothioate triester. As an example, the sequence analysis is presented of M13 phage DNA and of RNA prepared by transcription with SP6 RNA polymerase.
Chlamydia trachomatis Species-Specific Induction of Ezrin Tyrosine Phosphorylation Functions in Pathogen Entry (2007)

Chlamydia trachomatis is an obligate intracellular pathogen of humans that exhibits species-specific biological characteristics in its early interactions with host cells that are likely important to pathogenesis. One such characteristic is the tyrosine phosphorylation (Tyr-P) of an approximately 70-kDa polypeptide that occurs only after infection of mammalian cells by human strains. We sought to identify this protein because of its potential significance to the pathogenesis of human chlamydial infections. Using an immunoproteomic approach we identified the host protein ezrin, a member of the ezrin-radixin-moesin (ERM) protein family that serves as a physical link between host cell receptors and the actin cytoskeleton. Confocal microscopy studies showed colocalization of ezrin and actin at the tips and crypts of microvilli, the site of chlamydial attachment and entry, respectively. To demonstrate a functional role for ezrin we infected cells with a dominant-negative (DN) ezrin phenotype or treated cells with ezrin-specific small interfering RNA (siRNA). We found that both DN and siRNA-treated cells were significantly less susceptible to infection by human chlamydial strains. Moreover, we demonstrated that inhibition of infection in ezrin DN cells occurred at the stage of chlamydial entry. We hypothesize that the C. trachomatis-specific Tyr-P of ezrin might relate to an undefined species-specific mechanism of pathogen entry that involves chlamydial specific ligand(s) and host cell coreceptor usage.
The Scrapie Agent: Evidence Against its Dependence for Replication on Intrinsic Nucleic Acid (1978)

Exposure of the scrapie agent to u.v. light at various wavelengths has shown that light of 237 nm is 4 to 5 times as effective in inactivating it as 'germicidal' wavelengths (250 to 270 nm); whereas with systems that depend on RNA or DNA for function, inactivation is most effective by wavelengths in the germicidal range and there is a minimum of response in the wavelength region round 240 nm. The action spectrum for the scrapie agent is reminiscent of the absorption spectrum for purified bacterial endotoxin, identified as a lipopolysaccharide complex. Dilute aqueous suspensions of scrapie agent were exposed to ionizing radiations in the presence or absence of oxygen. In dilute suspensions of test systems depending on the integrity of nucleic acid or protein, oxygen is almost invariably protective, but it was extremely sensitizing for inactivation of the scrapie agent, to an extent approached only in the case of membranous systems like lysosomes. Results of these two methods argue against dependence of the scrapie agent on an intrinsic nucleic acid moiety for ability to replicate. They suggest that a lipid fraction is an important component and to that extent provide additional support for the 'membrane hypothesis'.
In vitro antibiotic release from poly(3-hydroxybutyrate-co-3-hydroxyvalerate) rods (2002)

Provision and maintenance of adequate concentrations of antibiotics at infection sites is very important in treating highly resistant infections. For diseases like implant related osteomyelitis (IRO) it is best to provide this locally via implanted drug formulations, as systemic administration of the antibiotic may not be effective due to damaged vasculature. In this study, poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) rods containing 7, 14 and 22% (mol) 3-hydroxyvalerate were loaded with sulbactam:cefoperazone or gentamicin, and their antibiotic release behaviours were studied under in vitro conditions in physiological phosphate buffer at room temperature. The release patterns were representative of release from monolithic devices where a rapid early release phase is followed by a slower and prolonged release. With PHBV 22 rods, the latter phase continued for approximately 2 months. This duration is critical because a proper antibiotic therapy of IRO requires the minimal effective concentration for at least 6 weeks. After in vitro release, voids with sharp edges were detected on the rods, indicating that the drug crystals dissolved but the polymer did not undergo erosion within this test period. Changing the polymer:drug ratio from 2:1 to 20:1 substantially decreased the drug release rate. A change of polymer type, however, did not lead to any detectable changes in the release patterns. Gentamicin release also followed a similar pattern, except that the concentration of the drug in the release medium exhibited a decrease after long release periods, indicating degradation (or decomposition) of the antibiotic in the release medium.
Erythropoietin: A Candidate Neuroprotective Agent in the Treatment of Glaucoma (2007)

Glaucoma is a progressive optic neuropathy that is the leading cause of irreversible blindness in the world. Although methods to lower intraocular pressure are the mainstay of glaucoma therapy, there are currently no available treatment modalities targeted at neuroprotection. Erythropoietin is a hematopoietic cytokine that has been shown to possess remarkable tissue-protective properties in preclinical models of neurodegeneration. As a result, there is a growing interest to explore the neuroprotective properties of erythropoietin as a possible therapeutic agent in neuropathic diseases of the eye such as glaucoma. Initial results in animal models have been promising, but further studies are needed to fully evaluate the safety and efficacy of this candidate neuroprotective agent in clinical trials.
Effects of barley variety fed to steers on carcass characteristics and color of meat (2004)

This study evaluated the effect of barley varieties in the diets of finishing steers on carcass composition, fat, and lean color and the fatty acid profile of subcutaneous fat. Crossbred steers (391 kg initial BW) were assigned randomly to one of five finishing diets composed primarily of corn (n = 9), Morex barley (n = 9), Steptoe barley, (n = 9), or two experimental barley varieties SM3 (n = 9) and SM5 (n = 9). Grains were cracked prior to feeding. Diets were formulated (DM basis) to be isonitrogenous (2.24% N) and isocaloric (2.01 Mcal/kg NEm and 1.35 Mcal/kg NEg). Steers were slaughtered according to industry-accepted procedures when it was visually estimated that 70% of carcasses would grade USDA Choice. After a 24-h chill at 4 degrees C, carcass quality and yield grade data were collected by trained, experienced university personnel. Objective color (L*, a*, and b*) of both the LM and subcutaneous fat were measured, and samples of subcutaneous fat were removed from the 10th- to 12th-rib region for fatty acid analysis. Diet did not affect hot carcass weight (P = 0.15), fat thickness (P = 0.58), LM area (P = 0.57), percentage of internal fat (P = 0.52), yield grade (P = 0.96), marbling (P = 0.73), or quality grade (P = 0.10). However, the LM from steers fed diets formulated with Morex and SM5 barley varieties tended to be lighter (higher L* values, P = 0.08) than the LM from steers fed the corn-based diet. Additionally, fat from steers fed corn tended to be more yellow (higher Hunter b* values, P = 0.09) than fat from steers fed barley-based diets. Although grain source had only minimal effects on the fatty acid composition of subcutaneous fat samples, pentadecanoic acid (15:0) was greater (P < 0.05) in fat from steers fed SM3 and Steptoe barley varieties than in fat from steers fed corn. Stearic acid (18:0) concentrations were higher (P < 0.05) in fat samples from steers fed corn than in those fed the experimental barley lines (SM3 and SM5). Conversely, fat samples from steers fed Steptoe and SM5 barley had greater (P < 0.05) gadoleic acid (20:1) concentrations than fat from steers fed corn or Morex variety. Although the variety/line of barley included in the finishing diet may affect LM and fat color, grain-source (barley vs. corn) had little effect on beef carcass quality and yield grades and did not greatly alter the fatty acid composition of subcutaneous fat.
The Role of the α2-Adrenoceptor Agonist Dexmedetomidine in Postsurgical Sedation in the Intensive Care Unit (2003)

Dexmedetomidine was evaluated for sedation of 401 post-surgical patients in this double-blind, randomized, placebo-controlled, multicenter trial. Dexmedetomidine or saline was started on arrival in the intensive care unit (ICU) (1.0 mcg/kg for 10 minutes), then titrated at 0.2 to 0.7 mcg/kg/h to effect. Patients could be given propofol if necessary. Morphine was administered for pain. Sixty percent of the dexmedetomidine patients required no other sedative to maintain an RSS > or = 3; 21% required < 50 mg propofol. In contrast, 76% of the control group received propofol; 59% required > or = 50 mg. Dexmedetomidine patients required significantly less morphine for pain relief (P <.001). Continuously given throughout the ICU stay, dexmedetomidine had no effect on respiratory rate, oxygen saturation, duration of weaning, or times to extubation. Nurses judged the dexmedetomidine patients were easier to manage. Later, fewer dexmedetomidine patients remembered pain or discomfort. The majority of dexmedetomidine patients maintained blood pressures within normal range, without rebound. Hypertension, atelectasis, and rigors occurred more frequently in the control group, while hypotension and bradycardia occurred more frequently in the dexmedetomidine group. Preoperative cardiovascular conditions were not risk factors for dexmedetomidine patients.
Oxidative stress during a 3.5-hour exposure to 120 kPa(a) PO2 in human divers. (1999)

We examined the effect of a prolonged dive on measures of oxidative stress in human divers. Ten subjects, wearing dry suits, completed mental tasks while lying quietly at 4.6 m fresh water for 3.5 h. Subjects (9 male, 1 female) were active, experienced divers ranging in age from 19 to 54 yr. Subjects breathed an enriched air nitrox mixture yielding a P(O2) of approximately 120 kPa(a) for the duration of the dive. Venous blood was drawn before and after the dive for measurements of hemoglobin (Hb), hematocrit (Hct), plasma osmolarity (O(SM)), red blood cell osmotic fragility (Frag), superoxide dismutase activity (SODa), and thiobarbituric acid reactive substances (TBARS). Plasma volume (PV) shifts were calculated from the changes in Hb and Hct. Significant increases in Hb, Hct, Osm, Frag, and TBARS were found along with significant decreases in PV and SODa (P < or = 0.05). We conclude that hyperbaric exposures encountered by technical divers are sufficient to cause significant oxidative stress.
Inflammation (1996)

National Institute of Neurological Disorders and Stroke, Office of the Director, Building 31, Room 8A62, 31 Center Drive MSC 2640, Bethesda, MD 20892–2640, USA
TINEA VERSICOLOR AND VISCERAL LEISHMANIASIS (1994)

Depressed cell-mediated immunity that is a feature of VL is the probable underlying cause for fungal infection. Tinea infection during the course of VL is to be distinguished from lesions of post-kala-azar dermal leishmaniasis.
The search for orally active medications through combinatorial chemistry (1998)

The literature of combinatorial chemistry is reviewed with particular attention paid to considerations of absorption, distribution, metabolism and excretion in the design and evaluation of libraries containing drug-like molecules. Published libraries are evaluated in particular for the likelihood that the products would possess oral bioavailability. © 1998 John Wiley & Sons, Inc. Med. Res. Rev., 18, No. 3, 149–185, 1998.
Growth, Metabolic, and Antibody Production Kinetics of Hybridoma Cell Culture: 2. Effects of Serum Concentration, Dissolved Oxygen Concentration, and Medium pH in a Batch Reactor (1991)

The effects of serum, dissolved oxygen (DO) concentration, and medium pH on hybridoma cell physiology were examined in a controlled batch bioreactor using a murine hybridoma cell line (167.4G5.3). The effect of serum was also studied for a second murine hybridoma cell line (S3H5/gamma 2bA). Cell growth, viability, cell density, carbohydrate and amino acid metabolism, respiration and energy production rates, and antibody production rates were studied. Cell growth was enhanced and cell death was decreased by increasing the serum level. The growth rates followed a Monod-type model with serum being the limiting component. Specific glucose, glutamine, and oxygen uptake rates and specific lactate and ammonia production rates did not change with serum concentrations. Amino acid metabolism was slightly influenced by the serum level. Cell growth rates were not influenced by DO between 20% and 80% air saturation, while the specific death rates were lowest at 20-50% air saturation. Glucose and glutamine uptake rates increased at DO above 10% and below 5% air saturation. Cell growth rate was optimal at pH 7.2. Glucose and glutamine uptake rates, as well as lactate and ammonia production rates, increased above pH 7.2. Metabolic rates for glutamine and ammonia were also higher below pH 7.2. The consumption or production rates of amino acids followed the glutamine consumption very closely. Cell-specific oxygen uptake rate was insensitive to the levels of serum, DO, and pH. Theoretical calculations based on experimentally determined uptake rates indicated that the ATP production rates did not change significantly with serum and DO while it increased continually with increasing pH. The oxidative phosphorylation accounted for about 60% of total energy production. This contribution, however, increased at low pH values to 76%. The specific antibody production rate was not growth associated and was independent of serum and DO concentrations and medium pH above 7.20. A 2-fold increase in specific antibody production rates was observed at pH values below 7.2. Higher concentrations of antibody were obtained at high serum levels, between 20% and 40% DO, and at pH 7.20 due to higher viable cell numbers obtained.
Exosome Mediated Delivery of Paclitaxel for the Treatment of Multi-Drug Resistant Pulmonary Metastases (2019)

Exosomes have recently come into focus as “natural nanoparticles” for use as drug delivery vehicles because they lack many drawbacks inherent to other nanoformulations. Many potentially useful chemotherapeutics possess undesirable attributes such as low solubility in aqueous solutions, immunogenicity, or inefficient accumulation in target cancer cells due to multidrug resistance (MDR) mechanisms. Our objective was to assess the feasibility of an exosome-based drug delivery platform for a potent chemotherapeutic agent, paclitaxel (PTX), to treat MDR cancers expressing the sigma receptor. Herein, we developed and compared different methods of loading exosomes released by macrophages with PTX (exoPTX), vectorized to target the sigma receptor (exoPTX-AA), and characterized their size, stability, drug release, and in vitro antitumor efficacy. A reformation of exosomes upon sonication resulted in high loading efficiency, and sustained drug release. Importantly, incorporation of PTX into exosomes increased cytotoxicity more than 50 times in drug resistant MDCKMDR1 (Pgp+) cells. Furthermore, exoPTX and exoPTX-AA demonstrated significantly greater cytotoxicity against all cell lines tested, as compared to Taxol and PTX. The biodistribution of exoPTX and exoPTX-AA and the antitumor effects of exoPTX were further evaluated in a model of murine Lewis Lung Carcinoma pulmonary metastases. Our studies demonstrated nearly complete co-localization of airway-delivered exosomes and intravenously delivered vectorized exosomes with cancer cells, and a potent anticancer effect of exoPTX in this mouse model. We conclude that exoPTX-AA holds significant potential for the delivery of various chemotherapeutics to treat drug resistant cancers.
Structure, Properties, and Preparation of Boronic Acid Derivatives (2011)

This chapter contains sections titled: Introduction and Historical Background Structure and Properties of Boronic Acid Derivatives Preparation of Boronic Acids and Their Esters Isolation and Characterization Overview of the Reactions of Boronic Acid Derivatives Overview of Other Applications of Boronic Acid Derivatives References
Cementing of Liners in Horizontal and High-Angle Wells at Prudhoe Bay, Alaska (1987)

ABSTRACT Standard Alaska Production Company has cemented liners in three horizontal and four high angle (inclination greater than 75°) wells at Prudhoe Bay, Alaska. Cementing techniques which have evolved during the drilling of these wells include off bottom cementing of 7 inch [17.8 cm] liners for gas cap isolation; simultaneous rotation and reciprocation of liners while cementing; and strategic placement of a cement filled formation packer between the gas/oil contact and the oil production interval. This paper describes the development of these cementing techniques and gives details of field operations.
The Diurnal Rhythm of Hypocretin in Young and Old F344 Rats (2004)

In old rats there is a 10% decline in CSF HCRT-1 over the 24-hour period. Functionally, if there is less HCRT-1, which our findings indicated, and there is also a decline in HCRT receptor mRNA, as has been previously found, then the overall consequence would be diminished action of HCRT at target sites. This would diminish the waking drive, which in the elderly could contribute to the increased tendency to fall asleep during the normal wake period.
Confocal scanning laser ophthalmoscope (1987)

A confocal scanning imager moves an illumination spot over the object and a (virtual) detector synchronously over the image. In the confocal scanning laser ophthalmoscope this is accomplished by reusing the source optics for detection. The common optical elements are all mirrors-either flat or spherical-and the scanners are positioned to compensate astigmatism due to mirror tilt. The source beam aperture at the horizontal scanner is small. Light returning from the eye is processed by the same elements, but now the polygon's facet is overfilled. A solid-state detector may be at either a pupillary or retinal conjugate plane in the descanned beam and still have proper throughput matching. Our 1-mm avalanche photodiode at a pupillary plane is preceded by interchangeable stops at an image (retinal) plane. Not only can we reject scattered light to a degree unusual for viewing the retina, but we choose selectively among direct and scattered components of the light returning from the eye. One (of many) consequences is that this ophthalmoscope gives crisp and complete retinal images in He-Ne light without dilation of the pupil.