gebhart/patrepeval huggingface dataset:
Tumor necrosis factor-alpha as a proliferative signal for an IL-2-dependent T cell line: strict species specificity of action. (1989)

The ability of TNF-alpha to stimulate T cell proliferation was examined. We demonstrate that murine rTNF-alpha induces the proliferation of CT6, a murine T cell line previously thought to be responsive only to IL-2. This activity appears to be the result of the direct action of murine rTNF-alpha on the CT6 cells because neither 1) murine IL-2 or murine IL-4, lymphokines also capable of inducing CT6 proliferation, were detected in culture supernatants from murine rTNF-alpha-treated CT6 cells nor 2) did antibodies specific for IL-2 or IL-4 inhibit murine rTNF-alpha-induced CT6 proliferation. Unlike many of the activities displayed by TNF-alpha, its ability to induce CT6 cell proliferation shows strict species specificity as indicated by the failure of human rTNF-alpha to stimulate these cells. Flow cytometric analysis and binding of radiolabeled TNF-alpha have indicated that receptors for TNF-alpha on these cells are specific for murine TNF-alpha. The ability of murine rTNF-alpha to induce the proliferation of certain T cell lines further indicates that this molecule plays an important role in regulation of T cell-mediated immune responses.
Fluorescence-activated sorting of totipotent embryonic stem cells expressing developmentally regulated lacZ fusion genes. (1992)

Murine embryonic stem (ES) cells were infected with a retrovirus promoter trap vector, and clones expressing lacZ fusion genes (LacZ+) were isolated by fluorescence-activated cell sorting (FACS). Of 12 fusion genes tested, 1 was repressed when ES cells were allowed to differentiate in vitro. Two of three lacZ fusion genes tested were passed into the germ line, indicating that FACS does not significantly affect stem cell totipotency. The pattern of lacZ expression observed in vivo was consistent with that seen in vitro. Both fusion genes were expressed in preimplantation blastulas. However, a fusion gene whose expression was unaffected by in vitro differentiation was ubiquitously expressed in day-10 embryos, while the other, which showed regulated expression in vitro, was restricted to cells located along the posterior neural fold, the optic chiasm, and within the fourth ventricle. These results demonstrate the utility of using promoter trap vectors in conjunction with fluorescence sorting to disrupt developmentally regulated genes in mice.
Characterization of a New Human Diploid Cell Strain, IMR-90 (1977)

A new human diploid fibroblast-like cell line has been established from lung tissue of a female fetus. This has been frozen away in large quantity and characterized for use in research and related purposes. This is the first of a planned series of human cell lines to be established, characterized, and banked in large quantity in support of the National Institute on Aging research and general cell biology.
The cannabinoid CB1 antagonists SR 141716A and AM 251 suppress food intake and food-reinforced behavior in a variety of tasks in rats (2003)

Cannabinoid CB1 receptor agonists, including delta-9-tetrahydrocannabinol (Delta 9-THC) (the main psychoactive ingredient in marijuana) have been shown to increase feeding in rats and humans. Conversely, it has been reported that acute administration of the CB1 receptor antagonist SR 141716A reduces food intake in rats. Based upon this observation, it has been suggested that CB1 antagonists could be useful as appetite suppressant drugs. The present studies were designed to provide a detailed examination of the effects of CB1 antagonists on food intake across a range of paradigms. Two CB1 antagonists (SR 141716A and AM 251) were administered to rats trained on fixed-ratio schedules with two different ratio requirements (fixed-ratio 1 and fixed-ratio 5). Both drugs produced a dose-dependent decrease in lever pressing, and had a relatively long duration of action (T1/2: SR 141716A, 15.1 h; AM 251, 22.0 h). Furthermore, intake of three diets with differing macronutrient composition (lab chow, high fat, high carbohydrate) was studied. Both drugs significantly suppressed intake of all three foods, and there were no significant interactions between drug dose and diet type. These findings support the hypothesis that CB1 receptor antagonists could be useful pharmacological tools for the suppression of appetite.
The dorsal medial prefrontal (anterior cingulate) cortex–amygdala aversive amplification circuit in unmedicated generalised and social anxiety disorders: an observational study (2014)

We track the functional role of a single neural circuit from its involvement in adaptive threat-biases under stress, to its chronic engagement in anxiety disorders in the absence of experimentally induced stress. Thus, we uniquely map a mood and anxiety related circuit across its adaptive and maladaptive stages. Clinically, this may provide a step towards a more mechanistic spectrum-based approach to anxiety disorder diagnosis and may ultimately lead to more targeted treatments.
Pervasive detection of process races in deployed systems (2011)

Process races occur when multiple processes access shared operating system resources, such as files, without proper synchronization. We present the first study of real process races and the first system designed to detect them. Our study of hundreds of applications shows that process races are numerous, difficult to debug, and a real threat to reliability. To address this problem, we created RacePro, a system for automatically detecting these races. RacePro checks deployed systems in-vivo by recording live executions then deterministically replaying and checking them later. This approach increases checking coverage beyond the configurations or executions covered by software vendors or beta testing sites. RacePro records multiple processes, detects races in the recording among system calls that may concurrently access shared kernel objects, then tries different execution orderings of such system calls to determine which races are harmful and result in failures. To simplify race detection, RacePro models under-specified system calls based on load and store micro-operations. To reduce false positives and negatives, RacePro uses a replay and go-live mechanism to distill harmful races from benign ones. We have implemented RacePro in Linux, shown that it imposes only modest recording overhead, and used it to detect a number of previously unknown bugs in real applications caused by process races.
Toxins VapC and PasB from Prokaryotic TA Modules Remain Active in Mammalian Cancer Cells (2014)

Among the great number of addictive modules which have been discovered, only a few have been characterized. However, research concerning the adoption of toxins from these systems shows their great potential as a tool for molecular biology and medicine. In our study, we tested two different toxins derived from class II addictive modules, pasAB from plasmid pTF-FC2 (Thiobacillus ferrooxidans) and vapBC 2829Rv (Mycobacterium tuberculosis), in terms of their usefulness as growth inhibitors of human cancer cell lines, namely KYSE 30, MCF-7 and HCT 116. Transfection of the pasB and vapC genes into the cells was conducted with the use of two different expression systems. Cellular effects, such as apoptosis, necrosis and changes in the cell cycle, were tested by applying flow cytometry with immunofluorescence staining. Our findings demonstrated that toxins VapC and PasB demonstrate proapoptotic activity in the human cancer cells, regardless of the expression system used. As for the toxin PasB, observed changes were more subtle than for the VapC. The level of expression for both the genes was monitored by QPCR and did not reveal statistically significant differences within the same cell line.
Heterodimerization of the transcription factors E2F-1 and DP-1 is required for binding to the adenovirus E4 (ORF6/7) protein (1994)

Adenovirus infection leads to E1A-dependent activation of the transcription factor E2F. E2F has recently been identified in complexes with cellular proteins such as the retinoblastoma protein (pRB) and the two pRB family members p107 and p130. E1A dissociates E2F from these cellular proteins, and another viral protein, E4 (ORF6/7), can bind to E2F. The binding of E4 to E2F induces the formation of a stable DNA-binding complex containing the two proteins, and stimulation of the adenovirus E2 early promoter can occur. Recent studies have shown that E2F is the combined activity of several proteins, and we demonstrate here that heterodimerization of two of these proteins, E2F-1 and DP-1, is required for stable binding to E4. This complex is formed independently of DNA binding and requires the C-terminal 20 amino acids of E4. Furthermore, the binding is dependent on a region of E2F-1 between amino acids 284 and 358. This region of E2F-1 is conserved in E2F-2 and E2F-3, and deletion of this region drastically reduces the transcriptional activity of the molecule without affecting DP-1 binding, suggesting that this region of the E2F transcription factors is involved in regulating their activity. Our experiments also demonstrate that pRB binding to the E2F-1/DP-1 heterodimer prevents the formation of an E2F-1/DP-1/E4 complex.
The world economy [October 2005] (2005)

The most recent economic data suggests that the recovery is strengthening in the US and the Asian economies (excluding Japan) but is weaker in the Euro Area and Japan. Global domestic demand remains relatively weak but is expected to pick up in the second half of this year. There are mixed signals from consumer confidence measures with some remaining weak while others are showing signs of improvement. The labour markets also demonstrate mixed performance. The unemployment rate fell in the US but so did the employment rate. Oil prices have remained flat but there is little evidence to suggest that the world economy is experiencing any significant inflationary pressures. There are clear signs however from central banks that interest rates will have to rise shortly. While the hostilities in Iraq were brought to a rapid conclusion there is now more concern over "guerrilla warfare" from disaffected Iraqis and opposition groups. This is not only potentially destabilising for the Middle East but adds to the uncertainty in the world economy.
Modulation of Coronary Collateral Angiogenesis: A Canine Model of Neovascularization Induced by Chronic Ischemia (1995)

Coronary collateral development in response to chronic myocardial ischemia is modulated by the integrated release of a variety of growth factors. Protamine, a specific inhibitor of angiogenesis in vitro and in vivo, may attenuate coronary collateral development. The purpose of this investigation was to characterize a model of canine coronary collateral development and to ascertain the effects of protamine on collateral perfusion in response to chronic myocardial ischemia. Ischemia-induced coronary collateral enhancement in response to daily, repetitive, 2-minute left anterior descending (LAD) coronary artery occlusions over 22 consecutive days was demonstrated in control (saline treated) dogs by time dependent, significant (p < 0.05) increases in collateral blood flow to ischemic myocardium. Concomitant with increases in collateral perfusion, myocardial contractile function during LAD occlusion was progressively normalized, and percent coronary flow repayment was reduced successively. These indicators of collateral development were attenuated significantly by administration of subcutaneous protamine. The present findings demonstrate that a model of brief, repetitive, coronary artery occlusion in chronically instrumented dogs sensitively elicits extensive enhancement of the coronary collateral circulation in response to chronic myocardial ischemia. In contrast, protamine attenuates coronary collateral development through its actions as an inhibitor of angiogenesis.
Rapid assay for evaluating the chemosensitivity of human tumors in soft agar culture. (1982)

Abstract Assays that measure [3H]thymidine incorporation by cells plated in soft agar were investigated to identify a rapid method for assessing chemosensitivity of tumor cells. Six established cell lines (five melanomas and one colon carcinoma) and cells prepared from 23 primary or metastatic tumors (ten melanomas, five colon adenocarcinomas, three lung carcinomas, two ovarian adenocarcinomas, one breast adenocarcinoma, and one leiomyosarcoma) were tested. The end point of tritium incorporation was measured by autoradiographs (labeling index) and scintillation counting (cpm) after 24-hr labeling. When results were compared, there was a strong correlation between the two assays (p However, the scintillation counting assay had major advantages: (a) counting incorporated radioisotope was technically easier than the autoradiographic method; (b) the DNA synthesis rate of the whole tumor cell population could be evaluated, not that of tumor colony-forming cells alone; and (c) the sampling error was minimized since the procedure was done automatically. There was significant association between cpm values 48 to 72 hr after plating and the number of colonies formed at 2 to 4 weeks in control dishes (p
Melt-extruded polyethylene oxide (PEO) rods as drug delivery vehicles: Formulation, performance as controlled release devices and the influence of co-extruded excipients on drug release profiles (2012)

The utility of controlled release medication formulations lies in their ability to keep drugs at steady levels in the blood plasma of recipients and within the termini of the maximum and minimum effective therapeutic levels. This avoids the “ups” and “downs” of medication levels within the body which would have been the result had conventional immediate release tablets been administered instead. In the veterinary field, controlled release medications are essential¹ because of the logistical difficulties of administering drugs on a regular (e.g., daily) basis to animals. The chief advantages of controlled release veterinary medications lie in the ease with which they can be administered; decrease in stress for animals, owing to less need for rounding up and frequent dosing; and, most importantly for farmers, the reduced cost of treatment relative to that for a multiple dosage regime.
Hartley transformation for hybrid pattern matching (1990)

A hybrid pattern matching system using the binary versions of the Hartley and related transformations is presented. These transformations can be obtained by an incoherent optical system described in this paper. Using them, the spurious correlation signals inherent in an incoherent pattern matching system based on the optical cosine transformation are removed. Experimental demonstrations in an incoherent-optical/digitalel ectronic hybrid system are also presented.
DNA capture by a CRISPR-Cas9–guided adenine base editor (2020)

CRISPR-Cas-guided base editors convert A•T to G•C, or C•G to T•A, in cellular DNA for precision genome editing. To understand the molecular basis for DNA adenosine deamination by adenine base editors (ABEs), we determined a 3.2-angstrom resolution cryo-electron microscopy structure of ABE8e in a substrate-bound state in which the deaminase domain engages DNA exposed within the CRISPR-Cas9 R-loop complex. Kinetic and structural data suggest that ABE8e catalyzes DNA deamination up to ~1100-fold faster than earlier ABEs because of mutations that stabilize DNA substrates in a constrained, transfer RNA-like conformation. Furthermore, ABE8e's accelerated DNA deamination suggests a previously unobserved transient DNA melting that may occur during double-stranded DNA surveillance by CRISPR-Cas9. These results explain ABE8e-mediated base-editing outcomes and inform the future design of base editors.
Two Decades of Research on Nano‐Energetic Materials (2014)

International audience
Preparation, Resolution, and Biological Evaluation of 5-Aryl-1,2-dihydro-5H-chromeno[3,4-f]quinolines:  Potent, Orally Active, Nonsteroidal Progesterone Receptor Agonists (1998)

Two potent nonsteroidal progestins from the 5-aryl-1, 2-dihydro-5H-chromeno[3,4-f]quinoline class (LG120746 and LG120747) were selected for scale-up, resolution, and biological evaluation of the purified enantiomers. For each quinoline, the levorotatory enantiomer was determined to be the more potent agonist of the human progesterone receptor isoform B (hPR-B) (EC50 < 3 nM), but the dextrorotatory enantiomers retained significant PR modulatory activity (EC50 < 200 nM). In two in vivo rodent models of progestational activity, a pregnancy maintenance assay and a uterine wet weight assay, the two eutomers displayed potent progesterone-like effects. In a third model for progestational activity, the mammary end bud assay, these compounds were significantly less active. These studies demonstrate that certain members of this class of selective progesterone receptor modulators display encouraging and potentially useful tissue-selective progestational effects.
Factors influencing the survival of cell monolayers during storage at 4 degrees. (1976)

As a step towards the definition of a medium suitable for long-term storage of potential organ transplants, a study was made of the effects of various solutions on the viability of monolayers of cells stored at 4 degrees. It was found that, for these to survive for more than a few hours, an essential component of the medium was a non-toxic solute which did not cross the cell membrane at low temperatures and could therefore counterbalance the osmotic effect of the intracellular proteins. A high K+/Na+ ratio and hyperosmoticity, separately or together, were ineffective in the absence ofsuch a solute and unnecessary in its presence. The most effective non-permeating solute tested was polyethylene glycol, mol. wt. 20,000 cells stored in a 1% solution of this in phosphate buffered balanced salt solution remained viable for at least 24 hours and could subsequently be grown in culture.
Collision avoidance for multiple agent systems (2004)

Techniques using gyroscopic forces and scalar potentials are used to create swarming behaviors for multiple agent systems. The methods result in collision avoidance between the agents as well as with obstacles.
The effect of electron beam irradiation on the survival of Salmonella enterica serovar typhimurium and psychrotrophic bacteria on raw chicken breasts stored at four degrees celsius for fourteen days (2005)

The effect of high-energy electron beam irradiation on the survival of Salmonella enterica serovar Typhimurium and psychrotrophic bacteria on commercial chicken breast meat was evaluated. Fresh chicken breast meat was purchased from a local poultry processor, inoculated with 8 log10 cfu/mL Salmonella, packaged in Styrofoam trays and over wrapped with a polyvinyl chloride film, and subjected to 0, 1, 2, or 3 kGy of irradiation. The packaged samples were stored at 4 degrees C and analyzed for Salmonella Typhimurium and psychrotrophic organisms at 0, 2, 4, 6, 8, 10, 12, and 14 d of storage. Direct plating and enrichment methods were used for S. Typhimurium analyses. The direct plating method revealed a 4 log reduction in Salmonella for chicken breasts inoculated and treated with 1, 2, or 3 kGy of irradiation. Psychrotrophic counts were conducted at 7 degrees C for 10 d and 25 degrees C for 5 d to determine the effect of incubation methods on the recovery of psychrotrophic organisms. The enrichment method resulted in the repair of injured Salmonella cells and an elevated Salmonella Typhimurium count for all irradiation dosages when compared with data reported for the direct plating method. In general, psychrotrophic counts increased as storage time increased. However, psychrotrophic counts decreased (P < 0.05) as the irradiation dosage increased.
Endometrial resection: a diagnostic tool in postmenopausal women (1999)

Objective To determine the diagnostic role of hysteroscopic endometrial resection in symptomatic postmenopausal women. Design Retrospective study. Setting Gynaecology department at a general hospital. Patients 150 postmenopausal women with abnormal uterine bleeding. Interventions Hysteroscopic transcervical resection of endometrium under general or spinal anaesthesia. Results Eight endometrial carcinomas were detected in endometrial chips and were managed with simple hysterectomy. A benign organic cause was noted in 131 cases, and 11 women had atrophic endometrium. All 142 postmenopausal women with a benign lesion were satisfied with their treatment and had no recurrence of abnormal bleeding during a mean follow up of 28 months. Conclusion Endometrial transcervical resection is a reasonable clinical strategy for single‐procedure evaluation and treatment in postmenopausal women with abnormal uterine bleeding.
Mannosylated Chitosan Nanoparticles for Delivery of Antisense Oligonucleotides for Macrophage Targeting (2014)

The therapeutic potential of antisense oligonucleotides (ASODN) is primarily dependent upon its safe and efficient delivery to specific cells overcoming degradation and maximizing cellular uptake in vivo. The present study focuses on designing mannosylated low molecular weight (LMW) chitosan nanoconstructs for safe ODNs delivery by macrophage targeting. Mannose groups were coupled with LMW chitosan and characterized spectroscopically. Mannosylated chitosan ODN nanoparticles (MCHODN NPs) were formulated by self-assembled method using various N/P ratio (moles of amine groups of MCH to phosphate moieties of ODNs) and characterized for gel retardation assay, physicochemical characteristics, cytotoxicity and transfection efficiency, and antisense assay. Complete complexation of MCH/ODN was achieved at charge ratio of 1:1 and above. On increasing the N/P ratio of MCH/ODN, particle size of the NPs decreased whereas zeta potential (ZV) increased. MCHODN NPs displayed much higher transfection efficiency into Raw 264.7 cells (bears mannose receptors) than Hela cells and no significant toxicity was observed at all MCH concentrations. Antisense assay revealed that reduction in lipopolysaccharide (LPS) induced serum TNF-α is due to antisense activity of TJU-2755 ODN (sequence complementary to 3'-UTR of TNF-α). These results suggest that MCHODN NPs are acceptable choice to improve transfection efficiency in vitro and in vivo.
Inhibition of establishment and growth of mouse liver metastases after treatment with interferon gamma and β-1,3-d-glucan (1998)

The purpose of this study was to investigate the combined antitumor effect of aminated beta-1,3-D-glucan (AG) and interferon-gamma (IFN-gamma) in an experimental liver metastasis model. Liver metastases were established by inoculation of C-26 colon carcinoma cells into the superior mesenteric vein of syngeneic mice. Treatment of mice started 24 hours after inoculation of tumor cells by daily intravenous injections of either AG, IFN-gamma, or a combination of both for a duration of 6 days. The resultant liver metastases were then quantified after an additional period of 11 days. Combination of IFN-gamma and AG inhibited the growth of liver metastases almost entirely. IFN-gamma was also very efficient, while AG alone did not exert any significant antitumor effect. These results, along with histological studies from mice receiving AG and IFN-gamma, indicated that activation and recruitment of liver macrophages may be a part of the mechanism responsible for the inhibition of metastatic growth observed in this study.
MONO- AND DIALKYLATION OF ISOPROPYL PHOSPHINATE-A SIMPLE PREPARATION OF ALKYLPHOSPHINATE ESTERS1 (1996)

Base-catalysed alkylation of isopropyl phosphinate with primary alkyl halides under mild conditions affords the corresponding alkyl phosphinate esters in fair to excellent yields.
Activity of the renin-angiotensin system in acute severe asthma and the effect of angiotensin II on lung function. (1994)

The renin-angiotensin system is activated in acute asthma and AII causes bronchoconstriction in vivo in man. These observations suggest that in some patients AII may contribute to bronchoconstriction during acute severe asthma.