gebhart/patrepeval huggingface dataset:
Characterization of H2 histamine receptor: linkage to both adenylate cyclase and [Ca2+]i signaling systems (1992)

We undertook these studies to examine the intracellular mechanisms of histamine action using a rat hepatoma-derived cell line that had been transfected to express the H2 histamine receptor cDNA. Transfected cells demonstrated increased adenosine 3',5'-cyclic monophosphate production, membrane inositol phospholipid turnover, and intracellular Ca2+ concentration ([Ca2+]i) in response to histamine. All of the effects could be inhibited with the H2 histamine receptor antagonist cimetidine, and the increased membrane inositol phospholipid turnover and [Ca2+]i were abolished by cholera toxin pretreatment of cells. These data support the notion that a single histamine H2 receptor can be linked to two stimulatory intracellular signaling systems.
Therapeutic effects of PKC activators in Alzheimer's disease transgenic mice (2004)

Alzheimer's disease (AD) characteristically presents with early memory loss. Regulation of K(+) channels, calcium homeostasis, and protein kinase C (PKC) activation are molecular events that have been implicated during associative memory which are also altered or defective in AD. PKC is also involved in the processing of the amyloid precursor protein (APP), a central element in AD pathophysiology. In previous studies, we demonstrated that benzolactam (BL), a novel PKC activator, reversed K(+) channels defects and enhanced secretion of APP alpha in AD cells. In this study we present data showing that another PKC activator, bryostatin 1, at subnanomolar concentrations dramatically enhances the secretion of the alpha-secretase product sAPP alpha in fibroblasts from AD patients. We also show that BL significantly increased the amount of sAPP alpha and reduced A beta 40 in the brains of APP[V717I] transgenic mice. In a more recently developed AD double-transgenic mouse, bryostatin was effective in reducing both brain A beta 40 and A beta 42. In addition, bryostatin ameliorated the rate of premature death and improved behavioral outcomes. Collectively, these data corroborate PKC and its activation as a potentially important means of ameliorating AD pathophysiology and perhaps cognitive impairment, thus offering a promising target for drug development. Because bryostatin 1 is devoid of tumor-promoting activity and is undergoing numerous clinical studies for cancer treatment in humans, it might be readily tested in patients as a potential therapeutic agent for Alzheimer's disease.
Endothelin-1 is an autocrine/paracrine growth factor for human cancer cell lines. (1991)

We studied whether a novel vasoconstrictor peptide, endothelin-1 (ET-1), is synthesized by and released from human carcinoma cell lines, and whether ET-1 stimulates proliferation of these tumor cells. ET-1-like immunoreactivity was released from both HeLa and HEp-2 cells as a function of time. Reverse-phase HPLC of the conditioned media from HeLa cells revealed a major peak coeluting with standard ET-1. Northern blot analysis demonstrated the expression of mRNA for ET-1 precursor in both tumor cell lines. Both cell lines contained a single class of specific binding sites for ET-1. ET-1 dose-dependently induced increases in cytosolic free Ca2+ concentration in fura-2-loaded tumor cells, whose effect was completely abolished by chelating extracellular Ca2+ or by Ca(2+)-channel blocker. ET-1 stimulated proliferation of the quiescent cell lines in a dose-dependent manner, whose effect was inhibited by Ca(2+)-channel blocker. Polyclonal antibody for ET-1 inhibited proliferation of these cell lines, whereas nonimmune serum had no effect. These results demonstrate that ET-1 is synthesized by and released from human epithelial carcinoma cell lines, and that exogenous and endogenous ET-1 stimulates proliferation of the cells possibly through Ca2+ influx, suggesting its role as an autocrine/paracrine growth factor for certain tumor cells.
Rhesus Cytomegalovirus Contains Functional Homologues of US2, US3, US6, and US11 (2005)

Human cytomegalovirus (HCMV) is a paradigm for mechanisms subverting antigen presentation by major histocompatibility complex (MHC) molecules. Due to its limited host range, HCMV cannot be studied in animals. Thus, the in vivo importance of inhibiting antigen presentation for the establishment and maintenance of infection with HCMV is unknown. Rhesus cytomegalovirus (RhCMV) is an emerging animal model that shares many of the features of HCMV infection. The recent completion of the genomic sequence of RhCMV revealed a significant degree of homology to HCMV. Strikingly, RhCMV contains several genes with low homology to the HCMV US6 gene family of inhibitors of the MHC I antigen presentation pathway. Here, we examine whether the RhCMV US6 homologues (open reading frames Rh182, -184, -185, -186, -187, and -189) interfere with the MHC I antigen-processing pathway. We demonstrate that Rh182 and Rh189 function similarly to HCMV US2 and US11, respectively, mediating the proteasomal degradation of newly synthesized MHC I. The US3 homologue, Rh184, delayed MHC I maturation. Unlike US3, MHC I molecules eventually escaped retention by Rh184, so that steady-state surface levels of MHC I remained unchanged. Rh185 acted similarly to US6 and inhibited peptide transport by TAP and, consequently, peptide loading of MHC I molecules. Thus, despite relatively low sequence conservation, US6 family-related genes in RhCMV are functionally closely related to the conserved structural features of HCMV immunomodulators. The conservation of these mechanisms implies their importance for immune evasion in vivo, a question that can now be addressed experimentally.
Comparison of Intron-Dependent and Intron-Independent Gene Expression (1988)

Recombinant simian virus 40 viruses carrying rabbit beta-globin cDNA failed to express the beta-globin sequence unless an intron was included in the transcription unit. The addition of either beta-globin IVS1 or IVS2 caused a 400-fold increase in RNA production. Stable beta-globin RNA production required sequences in IVS2 that were very close to the splice sites and that coincided with those needed for mRNA splicing. In addition to the recombinant viruses, intron-dependent expression was observed with both replicating and nonreplicating plasmid vectors in short-term transfections of cultured animal cells. Unlike transcriptional enhancer elements, IVS2 failed to increase stable RNA production when it was placed downstream of the polyadenylation site. Using a plasmid vector system to survey different inserted sequences for their dependence on introns for expression, we found that the presence of IVS2 stimulated the expression of these sequences 2- to 500-fold. Sequences from the transcribed region of the herpes simplex virus thymidine kinase gene, a gene that lacks an intervening sequence, permitted substantial intron-independent expression (greater than 100-fold increase) in the plasmid vector system.
Application of Robotics in General Surgery: Initial Experience (2004)

Robotic surgery was recently approved for clinical use in general abdominal surgery. The aim of this study was to review our experience with the da Vinci surgical system during laparoscopic general surgical procedures. Eighteen patients underwent robotically assisted laparoscopic abdominal surgery between June 2002 and March 2003. Main outcome measures were operative time, room setup time, robotic arm-positioning and surgical time, blood loss, conversion to laparoscopy, length of stay, and morbidity. The types of robotically assisted laparoscopic procedures were excision of gastric leiomyoma (n = 1), Heller myotomy (n = 1), cholecystectomy (n = 2), gastric banding (n = 2), Nissen fundoplication (n = 4), and gastric bypass (n = 8). The mean room setup time was 63 +/- 14 minutes, and the mean robotic arm-positioning time was 16 +/- 7 minutes. Conversion to laparoscopy occurred in two (11%) of 18 cases because of equipment difficulty (n = 1) and technical difficulty (n = 1). Estimated blood loss was 91 +/- 71 mL. The mean operative time was 156 +/- 42 minutes, and the robotic operative time was 27% of the total operative time. The mean length of hospital stay was 2.2 +/- 1.5 days. There was one postoperative wound infection and one anastomotic stricture. Robotically assisted laparoscopic abdominal surgery is feasible and safe; however, the theoretical advantages of the da Vinci surgical system were not clinically apparent.
Clinical and technical validation of a genomic classifier (ColoPrint) for predicting outcome of patients with stage II colon cancer. (2012)

384 Background: Between 25 and 35% of stage II colon cancer patients will experience a relapse of their disease and may benefit from adjuvant chemotherapy. ColoPrint is a gene expression classifier that can predict disease relapse in patients with early-stage colorectal cancer (Salazar et al. JCO 2011). Methods: ColoPrint was developed using gene expression data from whole genome microarrays and was validated in in-silico datasets and independent patient cohorts from 5 European hospitals. Fresh frozen tissues, clinical parameters, MSI-status and follow-up data for patients were available. Samples were hybridized to Agilent microarrays and the ColoPrint index was determined. Uni-and multivariate analysis was performed on the pooled stage II patient set (n=320) who had a median follow-up of 70 months. Reproducibility and precision studies were performed using clinical and control samples specific for each outcome level (high risk, low risk). Experiments were performed on 20 days with 2 runs per day by multiple technicians reflecting daily diagnostic conditions. Results: Performance of the prognostic classifier was confirmed in reproducibility and stability assays and stringent quality controls were established. In the clinical validation, ColoPrint classified two-third of patients (209/320) as low risk. The 3-year relapse-free survival was 94% for low risk patients and 79% for high risk patients with a HR of 2.74 (95% CI 1.54-4.88; p=0.006). MSI-status and the number of assessed lymph nodes were the only significant clinical parameters in the univariate analysis. Using parameters from the ASCO recommendation (T4, perforation, less than 12 LN assessed and/ or high grade) for the identification of high risk patients was not significant (HR 1.43, 95% CI 0.81-2.55; p= 0.22) and no clinical parameter added power to the ColoPrint classification in multivariate analysis. Conclusions: ColoPrint is available as a routine diagnostic test with a high precision and reproducibility. ColoPrint significantly improves the prognostic accuracy of pathologic factors and MSI and facilitates the identification of low risk patients with stage II disease who may be safely managed without chemotherapy.
NOVEL KINETIC ENERGY PENETRATORS FOR ELECTROMAGNETIC GUNS (2004)

Hypervelocity extending projectiles launched by electric guns are candidates for providing improved lethality to the Future Combat System (FCS). A systematic investigation of rod/tube type extending projectiles shows that optimal performance is achieved with roughly equal partitioning of mass between the two components and with a rod-first orientation. Potential reduction in muzzle energy for defeat of a fixed target is very substantial.
In breast cancer, amplification of the steroid receptor coactivator gene AIB1 is correlated with estrogen and progesterone receptor positivity. (1998)

The AIB1 gene was isolated upon microdissection of the homogeneously staining regions observed in breast cancer cell lines. It was subsequently shown to map at a region at 20q12 that is frequently amplified in breast tumors. In a screen of breast tumor cell lines, of all the genes mapping to the region, AIB1 appeared to be the most consistently amplified and overexpressed. AIB1 shares homology with the SRC-1 family of nuclear receptor coactivators. It was found to interact in a ligand-dependent manner with the estrogen receptor (ER) and to result in increased levels of estrogen-dependent transcription. These properties could be of important biological significance in breast and ovarian cancerigenesis, and we were, therefore, interested in determining whether the amplification of the AIB1 gene was associated with a particular phenotype or subgroup in these tumors. We tested a population of 1157 breast and 122 ovarian tumors in which DNA amplification had been determined previously at 15 chromosomal locations. Amplification of the AIB1 gene was observed in 4.8% of breast cancers and 7.4% of ovarian cancers. In breast tumors, AIB1 was correlated with ER and progesterone receptor positivity, as well as with tumor size. Correlation was also observed with the amplification of MDM2 and FGFR1 genes, but interestingly, no correlation was found with the amplification of CCND1, which is known to be strongly associated with ER. Furthermore, analyzing at 20q12-q13 range, we show the existence of three amplification cores, represented by AIB3/AIB4, AIB1, and RMC20C001. AIB1 and CCND1 amplifications may, thus, represent two different subsets of ER-positive breast tumors.
Isolation and functional characterization of Schwann cells derived from adult peripheral nerve (1991)

To facilitate the development of autologous transplantation techniques with which to test the ability of Schwann cell (ScC) implantations to treat nervous system injury, we have developed a method for procuring large, essentially pure populations of ScCs from adult peripheral nerve. By allowing small explants of peripheral nerve trunk to undergo axonal and myelin breakdown in vitro, rather than dissociating the nerve immediately after harvest, we are able to (1) rid the explant of nearly all fibroblasts and (2) capitalize on the intrinsic ScC mitogenic response to peripheral nerve degeneration. Here, we describe a method that yields up to 98% pure ScC populations from adult rat sciatic nerve (based on cell soma and nuclear morphology, S100 staining, and behavior of dissociated cells on neurites) at cell yields of greater than 2 x 10(4) cells/mg of starting nerve weight. The purification technique was successfully applied to human tissue; human phrenic nerve yielded 98% pure ScC populations at cell yields of 2 x 10(4) cells/mg of initial nerve weight. Similar to neonatally derived ScCs, adult rat cells can be expanded in coculture with dorsal root ganglion (DRG) neurons or in isolation in the presence of glial growth factor and forskolin. Cells expanded indefinitely on DRG neurons, or up to 10 weeks on chemical mitogens, return to quiescence following removal of the mitogenic stimulus. Expanded adult-derived rat ScCs retain functional capacity, as evidenced by their ability to myelinate DRG neurites and to support regeneration of processes from embryonic rat retinal explants.
Spectral differential imaging detection of planets about nearby stars (1987)

Direct ground-based optical imaging of planets in orbit about nearby stars may be accomplished by spectral differential imaging using multiple passband acoustooptic filters with a CCD. This technique provides two essential results. First, it provides a means to modulate the stellar flux reflected from a planet while leaving the flux from the star and other sources in the same field of view unmodulated. Second, spectral differential imaging enables the CCD detector to achieve a sufficiently high dynamic range to locate planets near a star in spite of an integrated brightness differential of 5 x 10 to the 8th. Spectral differential imaging at nearby diffraction limited imaging conditions with telescope apodization can reduce the time to conduct a sensitive planetary search to a few hours in some cases. The feasibility of this idea is discussed here and shown to provide, in principle, the discrimination and sensitivity to detect a Jovian-class planet about stars at distances of about 10 parsecs. The detection of brown dwarfs is shown to be feasible as well.
Approaches to automated protein crystal harvesting (2014)

The harvesting of protein crystals is almost always a necessary step in the determination of a protein structure using X-ray crystallographic techniques. However, protein crystals are usually fragile and susceptible to damage during the harvesting process. For this reason, protein crystal harvesting is the single step that remains entirely dependent on skilled human intervention. Automation has been implemented in the majority of other stages of the structure-determination pipeline, including cloning, expression, purification, crystallization and data collection. The gap in automation between crystallization and data collection results in a bottleneck in throughput and presents unfortunate opportunities for crystal damage. Several automated protein crystal harvesting systems have been developed, including systems utilizing microcapillaries, microtools, microgrippers, acoustic droplet ejection and optical traps. However, these systems have yet to be commonly deployed in the majority of crystallography laboratories owing to a variety of technical and cost-related issues. Automation of protein crystal harvesting remains essential for harnessing the full benefits of fourth-generation synchrotrons, free-electron lasers and microfocus beamlines. Furthermore, automation of protein crystal harvesting offers several benefits when compared with traditional manual approaches, including the ability to harvest microcrystals, improved flash-cooling procedures and increased throughput.
Effect of whole-body hyperthermia and cyclophosphamide on natural killer cell activity in murine erythroleukemia. (1988)

Mice infected with the polycythemia-inducing strain of Friend virus complex (FVC-P) develop a fatal erythroid disease similar in some respects to leukemia. Six- to eight-week-old DBA/2 female mice were injected i.v. with 0.5 ml of a virus suspension containing approximately 5 X 10(4) plaque-forming units and 5 X 10(3) spleen focus-forming units. Four treatment regimens were begun 3 days postinjection: (a) no treatment; (b) whole-body hyperthermia (WBH) alone; (c) cyclophosphamide (CY) alone; (d) WBH combined with CY. WBH treatment utilized a microwave generator operating at 2450 MHz. The i.p. temperature of the mice receiving WBH was maintained at 39.5-40 degrees C for 30 min. The CY was given i.p. at a dosage of 20 mg/kg of body weight. The various treatments, CY, WBH, CY + WBH were given once a week for 2 weeks. Natural killer cell activity was examined in all four groups of mice and was found to be significantly higher in the animals treated with WBH or CY. Our results show that WBH, either alone or in combination with CY, can prolong the lifespan of mice infected with lethal dosages of the FVC-P, possibly via a mechanism involving natural killer cells.
CELLULAR BIOLOGY OF BONE RESORPTION (1993)

Past knowledge and the recent developments on the formation, activation and mode of action of osteoclasts, with particular reference to the regulation of each individual step, have been reviewed. The following conclusions of consensus have emerged. 1. The resorption of bone is the result of successive steps that can be regulated individually. 2. Osteoclast progenitors are formed in bone marrow. This is followed by their vascular dissemination and the generation of resting preosteoclasts and osteoclasts in bone. 3. The exact pathways of differentiation of the osteoclast progenators to mature osteoclasts are debatable, but there is clear evidence that stromal cells support osteoclast generation. 4. Osteoclasts are activated following contact with mineralized bone. This appears to be controlled by osteoblasts that expose mineral to osteoclasts and/or release a factor that activates these cells. 5. Activated osteoclasts dissolve the bone mineral and digest the organic matter of bone by the action of agents secreted in the segregated microcompartments underlying their ruffled borders. The mineral is solubilized by protons generated from CO2 by carbonic anhydrase and secreted by an ATP-driven vacuolar H(+)-K(+)-ATPase located at the ruffled border. The organic matrix of the bone is removed by acid proteinases, particularly cysteine-proteinases that are secreted together with other lysosomal enzymes in the acid environment of the resorption zone. 6. Osteoclastic bone resorption is directly regulated by a polypeptide hormone, calcitonin (CT), and locally, by ionized calcium (Ca2+) generated as a result of osteoclastic bone resorption. 7. There is new evidence that osteoclast activity may also be influenced by the endothelial cells via generation of products including PG, NO and endothelin.
Microbes as tools for cell biology (1994)

Manipulation of pathogens microbial adherence and invasion assays the study of intracellular pathogenesis.
IL-12 Deaths: Explanation and a Puzzle (1995)

Researchers investigating toxic reactions that killed two patients in a trial of interleukin-12 earlier this year have reached a surprising conclusion: The drug is highly toxic if it is given in multiple high doses, but those effects can be avoided if the multiple doses are preceded by a single dose followed by a rest period. The initial dose apparently imprints a memory on the immune system, but the mechanism is unclear.
Design Considerations for Frequency Responsive Grid Friendly>sup<TM>/sup< Appliances (2006)

This paper addresses design considerations for frequency responsive grid friendlytrade appliances (FR-GFAs), which can turn on/off based on frequency signals and make selective low-frequency load shedding possible at appliance level. FR-GFAs can also be treated as spinning reserve to maintain a load-to-generation balance under power system normal operation states. The paper first presents a statistical analysis on the frequency data collected in 2003 in Western Electricity Coordinating Council (WECC) systems. Using these frequency data as an input, the triggering frequency and duration of an FR-GFA device with different frequency setting schemes are simulated. Design considerations of the FR-GFA are then discussed based on simulation results
Self-Assembly of an Operating Electrical Circuit Based on Shape Complementarity and the Hydrophobic Effect (1998)

The biomimetic self-assembly of an operating electrical circuit is described. The circuit, self-assembled via the hydrophobic effect from two different, but shape-complementary, non-functional subunits, contains a light-emitting diode (LED), a gold cathode, and a magnesium anode. It is shown that the system, when immersed in a suitable electrolyte (potassium ferricyanide), constitutes an electrochemical cell—the LED is powered through a reaction involving the dissolution of magnesium(0) at the anode and the reduction of ferricyanide to ferrocyanide at the cathode.
Photoprotection and Other Responses of Plants to High Light Stress (1992)

PHOTO PROTECTION 604 Prevention oj Excessive Light Absorption... 604 Removal of Excess Excitation Energy Directly within the Light-Capturing System ......... ...... . . ..... ..... . .... . ..... ...... .... . .. . .. . . ..... . . . ... ... . 604 Removal oj Active Oxygen Formed in the Photochemical Apparatus ........ . . .. . . . . . . 605 INACTIV A TIONiTURNOVER OF PS II 606 THE XANTHOPHYLL CYCLE AND THERMAL ENERGY DISSIPATION: A PHOTOPROTECTIVE RESPONSE 608 Characteristics oj the Xanthophyll Cycle . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . 608 Association Among the De-epoxidized State oj the Xanthophyll Cycle, Thermal Energy Dissipation. and Photoprotection .. .. . . . .. . . ...... .. .. ... ... 609 Operation of the Xanthophyll Cycle in the Field . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . .... . . . .. . . . . 611 CONCLUSIONS 618