588 research outputs found

    Program documentation standards

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    A style manual is presented to serve as a reference and guide for system and program documentation. It is intended to set standards for documentation, prescribing the procedures to be followed, format to be used, and information to be produced. The standards for program documentation specify the extent to which the programmer should support his efforts in writing. The first three sections of the manual (system, program, and operation descriptions) contain information of particular interest to management, operators, and program users, respectively. Each section was designed as a self-sufficient description from the management, operator, or user point of view

    Mutant p53 establishes targetable tumor dependency by promoting unscheduled replication

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    Gain-of-function (GOF) p53 mutations are observed frequently in most intractable human cancers and establish dependency for tumor maintenance and progression. While some of the genes induced by GOF p53 have been implicated in more rapid cell proliferation compared with p53-null cancer cells, the mechanism for dependency of tumor growth on mutant p53 is unknown. This report reveals a therapeutically targetable mechanism for GOF p53 dependency. We have shown that GOF p53 increases DNA replication origin firing, stabilizes replication forks, and promotes micronuclei formation, thus facilitating the proliferation of cells with genomic abnormalities. In contrast, absence or depletion of GOF p53 leads to decreased origin firing and a higher frequency of fork collapse in isogenic cells, explaining their poorer proliferation rate. Following genome-wide analyses utilizing ChIP-Seq and RNA-Seq, GOF p53–induced origin firing, micronuclei formation, and fork protection were traced to the ability of GOF p53 to transactivate cyclin A and CHK1. Highlighting the therapeutic potential of CHK1’s role in GOF p53 dependency, experiments in cell culture and mouse xenografts demonstrated that inhibition of CHK1 selectively blocked proliferation of cells and tumors expressing GOF p53. Our data suggest the possibility that checkpoint inhibitors could efficiently and selectively target cancers expressing GOF p53 alleles

    A President’s Influence on Student Activism

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    Following President Nixon’s announcement of the US military’s incursion into Cambodia, an eruption of innumerable student protests occurred all throughout colleges and universities across the United States in May 1970. The measure of violence displayed at these demonstrations, however, undoubtedly varied due to disparate surroundings and events specific to the atmosphere of these colleges. Evaluating the many contrasting occurrences that took place at different universities validates how the combined extensive preparation of the university’s president and administration have a beneficial effect on the level of violence shown at a protest on a college campus. With much preparation and steps taken towards preventative measures, President Robert E. Kennedy of California Polytechnic State University in San Luis Obispo “through foresight and planning insured that no one’s right of free speech was abridged and that no one overstepped the bounds of proper conduct in a free society.” The events at Kent State in Kent, Ohio proceeded otherwise. Under the presidency of Robert White, Kent State experienced four days of intense protest—resulting in the shooting of four students in addition to leaving nine students brutally injured on May 4, 1970. This paper will thoroughly compare Cal Poly’s administration to the administration of Kent State—predominantly focusing in on each staffs’ intentions regarding preparation for protests taking place during a critical moment. Taking a deeper glimpse into Robert E. Kennedy as a president and leader of Cal Poly’s campus, this paper will allow us to understand his capability of managing a protest that, as he put it in a memorandum to campus staff, “could easily have ignited into an unruly mob with violent action resulting in injury to people and damage to property.”2 Recognizing that this protest could have undeniably resulted in a similar outcome to that of Kent State, this paper will investigate the specific precautions and approaches that were taken to assure its peaceful conclusion. Additionally, this research will focus on the administrations and the presidencies of both Kent State and Cal Poly—exploring their similarities and differences

    Anticoagulant profile of subcutaneous enoxaparin in healthy dogs

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    Enoxaparin, a low-molecular-weight heparin, is commonly used as an anticoagulant in dogs, and is currently dosed at 0.8mg/kg every 6 hours. With an increase in individual enoxaparin doses, less frequent dosing may be possible, thereby reducing owner inconvenience and expense. The three phases of this study investigated the appropriate dose (Phase one- 0.8mg/kg, SQ once; Phase two- 2mg/kg, SQ once; Phase three- 1.3 mg/kg, SQ q8h for 7 total doses) and dosing interval needed for maximum effectiveness of enoxaparin. A Sonoclot® analyzer and factor Xa activity were used to assess level of anticoagulation in six healthy dogs. Anticoagulation was inconsistent at the 0.8mg/kg dose, while the 2mg/kg dose showed a high level of anticoagulation, and the 1.3mg/kg dose provided more reliable anticoagulation than the other dosages and dosing intervals. Small sample size and the use of same-breed healthy dogs potentially affected the strength of the results

    Adult Criminal Offense Trends Following Juvenile Delinquency

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    Use of the skin sandwich technique to probe the role of the hair follicles in sonophoresis

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    The human skin sandwich technique was used to explore the effect of brief ultrasound exposure on the transfollicular pathway of absorption. Hydrocortisone was used as a model drug. In order to calculate the permeability coefficient of hydrocortisone, its concentration at saturation in the PBS donor solution was determined. Skin samples were prepared by sandwich technique with total hydration of the epidermal and sandwich membranes. The skin was sonicated for 0 s (control), 30 s or 45 s using a pulsed mode (10% duty cycle) with the spatial and temporal average intensity (SATA) of 3.7 W/cm2. The transducer was then removed and permeation was allowed to proceed for 52 h. Then the percentage follicular contribution was determined. It was determined that without ultrasound, drug entry into follicles accounted for 46% of total penetration. As the duration of sonication increased, the follicular contribution fell to zero even though total transepidermal flux dramatically increased. This is explained by ultrasound exposure causing sloughing off of the uppermost stratum corneum. This permeabilises the continuous surface but at the same time the disturbed cornceocytes will plug hair follicle orifice

    The rovibrational spectrum of BeH, MgH and CaH at high temperatures in the X2Σ+X\,{}^2\Sigma^+ state: a theoretical study

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    Accurate line lists for three molecules, BeH, MgH and CaH, in their ground electronic states are presented. These line lists are suitable for temperatures relevant to exoplanetary atmospheres and cool stars (up to 2000K). A combination of empirical and \textit{ab initio} methods is used. The rovibrational energy levels of BeH, MgH and CaH are computed using the programs Level and DPotFit in conjunction with `spectroscopic' potential energy curves (PECs). The PEC of BeH is taken from the literature, while the PECs of CaH and MgH are generated by fitting to the experimental transition energy levels. Both spin-rotation interactions (except for BeH, for which it is negligible) and non-adiabatic corrections are explicitly taken into account. Accurate line intensities are generated using newly computed \textit{ab initio} dipole moment curves for each molecule using high levels of theory. Full line lists of rotation-vibration transitions for 9^9BeH, 24^{24}MgH, 25^{25}MgH, 26^{26}MgH and 40^{40}CaH are made available in an electronic form as supplementary data to this article and at \url{www.exomol.com}.Comment: MNRAS (in press

    Antioxidant and anti-lipoxygenase activities of extracts from different parts of Lavatera cretica L. grown in Algarve (Portugal)

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    Background: Lavatera cretica L. was used in folk medicine as anti-inflammatory among other applications. As inflammation is many times associated with oxidative processes, the aim of the present work was to evaluate the ability of aqueous extracts obtained from different parts of L. cretica to prevent oxidation or inflammation using several methods in vitro. Materials and Methods: The capacity of samples for preventing lipid peroxidation, scavenging free radicals, chelating metal ions, reducing power, and inhibiting lipoxygenase activity was investigated. This last assay also permits to evaluate the anti-inflammatory activity. The quantification of total phenols was performed using Folin-Chiocalteu reagent. Results: The highest concentrations of total polyphenols and flavonoids were found in the leaf extract (254.62 6.50 mg gallic acid equivalent/gram; dry weight). Leaf and flower extracts were the most active for scavenging 2,2-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt free radicals [Inhibition concentration (IC 50 = 2.88 0.54 and IC50 = 4.37 0.54 g/mL, respectively)], and leaf extract was also the best for scavenging hydroxyl radicals (IC 50 = 0.81 0.05 g/mL). Bract plus sepal extract possessed the best capacity for preventing lipid peroxidation when lecithin liposome was the lipid substrate (IC 50 = 0.19 0.03 g/mL) and scavenging superoxide anion radicals (IC 50 = 1.13 0.48 g/mL). Leaf and flower extracts were the best lipoxygenase inhibitors (IC 50 = 0.013 0.0034 g/mL in both extracts). Conclusions: L. cretica extracts were able to scavenge free radicals, inhibit lipid peroxidation and lipoxygenase activity. With these attributes, this plant can have an important role in the treatment of neurodegenerative disorders
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