Lack of functional retinoblastoma protein mediates increased resistance to antimetabolites in human sarcoma cell lines.

Growth inhibition assays indicated that the IC50 values for methotrexate (MTX) and 5-fluorodeoxyuridine (FdUrd) in HS-18, a liposarcoma cell line lacking retinoblastoma protein (pRB), and SaOS-2, an osteosarcoma cell line with a truncated and nonfunctional pRB, were 10- to 12-fold and 4- to 11-fold higher, respectively, than for the HT-1080 (fibrosarcoma) cell line, which has wild-type pRB. These Rb-/- cell lines exhibited a 2- to 4-fold increase in both dihydrofolate reductase (DHFR) and thymidylate synthase (TS) enzyme activities as well as a 3- to 4-fold increase in mRNA levels for these enzymes compared to the HT-1080 (Rb+/+) cells. This increase in expression was not due to amplification of the DHFR and TS genes. Growth inhibition by MTX and FdUrd was increased and DHFR and TS activities and expression were correspondingly decreased in Rb transfectants of SaOS-2 cells. In contrast, there was no significant difference in growth inhibition among these cell lines for the nonantimetabolites VP-16, cisplatin, and doxorubicin. A gel mobility-shift assay showed that parental SaOS-2 cells had increased levels of free E2F compared to the Rb-reconstituted SaOS-2 cells. These results indicate that pRB defective cells may have decreased sensitivity to growth inhibition by target enzymes encoded by genes whose transcription is enhanced by E2F proteins and suggest mechanisms of interaction between cytotoxic agents and genes involved in cell cycle progression.

Lack of bipolar see-saw in response to Southern Ocean wind reduction

A cessation of the Atlantic meridional overturning circulation (AMOC) significantly reduces northward oceanic heat transport. In response to anomalous freshwater flux, this leads to the classic 'bipolar see-saw' pattern of northern cooling and southern warming in surface air and ocean temperatures. By contrast, as shown here in a coupled climate model, both northern and southern cooling are observed for an AMOC reduction in response to reduced wind stress in the Southern Ocean (SO). For very weak SO wind stress, not only the overturning circulation collapses, but sea ice export from the SO is strongly reduced. Consequently, sea ice extent and albedo increase in this region. The resulting cooling overcompensates the warming by the reduced northward heat transport. The effect depends continuously on changes in wind stress and is reversed for increased winds. It may have consequences for abrupt climate change, the last deglaciation and climate sensitivity to increasing atmospheric CO_2 concentration.

Level of involvement of clinical nurses in the evaluation of competence of nursing students

Objective. To determine the level of involvement of clinical nurses accredited by the Universitat Jaume I (Spain) as mentors of practice (Reference Nurses) in the evaluation of competence of nursing students. Methodolgy. Cross-sectional study, in which the “Clinical Practice Assessment Manual” (CPAM) reported by reference 41 nurses (n=55) were analyzed. Four quality criteria for completion were established: with information at least 80% of the required data, the presence of the signature and final grade in the right place. Verification of learning activities was also conducted. Data collection was performed concurrently reference for nurses and teachers of the subjects in the formative evaluations of clinical clerkship period in the matter “Nursing Care in Healthcare Processes “, from March to June 2013. Results. 63% of CPAM were completed correctly, without reaching the quality threshold established (80%). The absence of the signature is the main criteria of incorrect completion (21%). Nine learning activities do not meet the quality threshold set (80%) (p < 0.05). There are significant differences according to clinical units p < 0.05. From the 30 learning activities evaluated in the CPAM, it can be stated that nine of them do not reach the verification threshold established (80%), therefore it cannot be assumed that these activities had been completed by students and evaluated by the RefN throughout the clinical clerkship period. Conclusion. The level of involvement of Reference Nurse cannot be considered adequate, although strategies to encourage involvement through collaboration and training must be developed.

Under the veneer of decentralisation. Ukraine's modernisation efforts stall due to lack of local government reform. OSW Commentary No. 102, 2013-02-12

President Viktor Yanukovych and his Party of Regions have been repeating the pledge to decentralise power in Ukraine and to give local government a greater decision-making role ever since the party appeared on the Ukrainian political scene. The implementation of this reform is crucial both for the economic recovery of Ukraine’s regions and the overall modernisation efforts of the Ukrainian state. At present relations between central government and the regions are regulated by Soviet-era legislation that fails to address the modern-day challenges facing Ukraine. The political elite in the country, including the opposition, appear to have reached consensus on the importance of the decentralisation reform. The first attempts to implement changes in this area were made in the late 1990s, followed by a comprehensive reform programme developed between 2007 and 2009 by Yulia Tymoshenko’s government. In 2012, the Constitutional Assembly under the President of Ukraine appointed a team of experts who drafted a document detailing the reform of local government and the territorial organisation of power1. The document envisages the implementation of what effectively are two major reforms: (1) an administrative-territorial reform, which would help consolidate the fragmented administrative structure, creating larger and more economically self-sufficient administrative units, and (2) local government reform, focusing on creating clearly defined powers for local authorities with a view to securing government funding for specific tasks delegated from central government. Nonetheless, despite these measures, and in spite of the rhetoric coming from President Yanukovych and other members of the Party of Regions, it seems unlikely that the reform will be implemented in the foreseeable future. A series of concrete political decisions taken by the president over the past three years indicate that Yanukovych has not abandoned his plan to build a highly centralised political system. This in turn limits the capacity to govern of local authorities and further restricts the sources of funding for Ukraine’s regions. This apparent resistance to change stems from the fact that by implementing the proposed reforms, the president and his political allies would be forced to relinquish much of their control over the political processes taking place in the country and would have to free up the distribution of budgetary resources between Kyiv and the regions. The implementation of the reform within the specified timeframe (i.e. by 2015) is also unlikely due to the upcoming presidential election and the deteriorating economic situation in Ukraine. Without a comprehensive reform of local government, however, Ukraine will be unable to undertake effective modernisation measures, which are key for the socio-economic development of the country’s regions.

Hypokinetic disease, diseases produced by lack of exercise,

Includes bibliography.

Hypokinetic disease; diseases produced by lack of exercise,

Includes bibliography.

The Dack family; a study in hereditary lack of emotional control,

Mode of access: Internet.

The lack of definite individual responsibility in our form of government is a fundamental cause of the evils of which the people complain : annual address before Bar Association of State of Kansas, delivered at Topeka, Kansas, January 27, 1913 /

Cover title.

Military base closures : lack of data inhibits cost-effectiveness analyses of privatization-in-place initiatives : report to the Chairman, Subcommittee on Military Readiness, Committee on Armed Services, House of Representatives /

"B-283515"--P. 3.

Lack of health insurance coverage in the United States : field hearing before the Subcommittee on Health of the Committee on Finance, United States Senate, One Hundredth Congress, second session.

"July 25, 1988"--Pt. 2.

Health care costs and lack of access to health insurance : hearings before the Committee on Finance, United States Senate, One Hundred Second Congress, first session.

"April 9 and 16, 1991"--Pt. 1; "June 6, 1991"--Pt. 2.

Lack of intraspecific biological variation between two geographical populations of Oomyzus sokolowskii (Hymenoptera: Eulophidae), a gregarious larval–pupal parasitioid of Plutella xylostella (Lepidoptera: Plutellidae)

The chalcid, Oomyzus sokolowskii Kurdjumov has been recorded in many parts of the world as a major larval-pupal, gregarious endoparasitoid of the diamondback moth, Plutella xylostella (Linnaeus), a serious pest of brassica vegetable crops worldwide. This study investigated intraspecific variation between two populations of O. sokiolowskii, one from Cape Verde Islands, West Africa and the other from Hangzhou, China. In all crosses and backcrosses between the two geographical populations, the numbers of progeny and sex ratio of progeny were similar to those obtained within each of the populations, demonstrating complete reproductive compatibility between the two populations. The two populations showed similar responses to temperature with respect to development time and survival of immature stages. Observations on the interactions between the two O. sokolowskii populations and Cotesia plutellae (Kurdjumov), another major parasitoid of P. xylostella, showed that neither population could achieve successful parasitism of P. xylostella larvae already parasitized by C. plutellac. However, both O. sokolowskii populations could achieve hyperparasitism by ovipositing into a mid-late stage larva of C. plutellae developing inside the primary host. Contrary to earlier reports, no evidence of intraspecific variations in ability to hyperparasitize between these two populations of O. sokolowskii was found.