The signaling axis atypical protein kinase C λ/ι-Satb2 mediates leukemic transformation of B-cell progenitors.

Epigenetically regulated transcriptional plasticity has been proposed as a mechanism of differentiation arrest and resistance to therapy. BCR-ABL leukemias result from leukemic stem cell/progenitor transformation and represent an opportunity to identify epigenetic progress contributing to lineage leukemogenesis. Primary human and murine BCR-ABL+ leukemic progenitors have increased activation of Cdc42 and the downstream atypical protein kinase C (aPKC). While the isoform aPKCζ behaves as a leukemic suppressor, aPKCλ/ι is critically required for oncogenic progenitor proliferation, survival, and B-cell differentiation arrest, but not for normal B-cell lineage differentiation. In vitro and in vivo B-cell transformation by BCR-ABL requires the downregulation of key genes in the B-cell differentiation program through an aPKC λ/ι-Erk dependent Etv5/Satb2 chromatin repressive signaling complex. Genetic or pharmacological targeting of aPKC impairs human oncogenic addicted leukemias. Therefore, the aPKCλ/ι-SATB2 signaling cascade is required for leukemic BCR-ABL+ B-cell progenitor transformation and is amenable to non-tyrosine kinase inhibition.

Effortless creation of safe robots from modules through self-programming and self-verification.

Industrial robots cannot be reconfigured to optimally fulfill a given task and often have to be caged to guarantee human safety. Consequently, production processes are meticulously planned so that they last for long periods to make automation affordable. However, the ongoing trend toward mass customization and small-scale manufacturing requires purchasing new robots on a regular basis to cope with frequently changing production. Modular robots are a natural answer: Robots composed of standardized modules can be easily reassembled for new tasks, can be quickly repaired by exchanging broken modules, and are cost-effective by mass-producing standard modules usable for a large variety of robot types. Despite these advantages, modular robots have not yet left research laboratories because an expert must reprogram each new robot after assembly, rendering reassembly impractical. This work presents our set of interconnectable modules (IMPROV), which programs and verifies the safety of assembled robots themselves. Experiments show that IMPROV robots retained the same control performance as nonmodular robots, despite their reconfigurability. With respect to human-robot coexistence, our user study shows a reduction of robot idle time by 36% without compromising on safety using our self-verification concept compared with current safety standards. We believe that by using self-programming and self-verification, modular robots can transform current automation practices.

Association of State-Mandated Abstinence-only Sexuality Education with Rates of Adolescent HIV Infection and Teenage Pregnancy.

INTRODUCTION: Abstinence-only sexuality education (AOSE); is required in the public school systems of many states, raising public health concerns and perpetuating health disparities through school systems. This study aimed to determine the correlations between state-mandated AOSE and the rates of adolescent HIV and teen pregnancy. METHODS: Using publicly available data on all 50 United States' laws and policies on AOSE, states were ranked according to their level of abstinence emphasis on sexuality education (Level 0 - Level 3);. We calculated the relative proportion of Black students in public schools and the proportion of families below the federal poverty line then ranked them by state. We compared the states' ranks to the incidence of adolescent HIV and teen pregnancy in those states to identify associations between variables. RESULTS: The majority of states (~44 percent ); have legally mandated AOSE policies (Level 3); and adolescent HIV and teen pregnancy rates were highest in these Level 3 states. There were significant, positive correlations between HIV incidence rates of 13-19 year olds, HIV rates of 20-24 year olds, teen pregnancy rates, and AOSE level, with the proportion of the population that lives below the federal poverty level, and whether they attended schools that had a greater than 50 percent of an African American population. DISCUSSION: These data show a clear association between state sexuality education policies and adolescent HIV and teen pregnancy rates not previously demonstrated. Our data further show that states that have higher proportions of at-risk populations, with higher adolescent HIV and teen pregnancy rates, are more likely to also have restrictive AOSE policies. These populations may be more likely to attend public schools where AOSE is taught, increasing their risk for HIV and teen pregnancy. The World Health Organization considers fact-based Comprehensive Sexuality Education a human right, and the authors believe it is past time to end harmful, discriminatory sexuality education policies in US public schools.

[Ambulatory prevention of thrombosis with low molecular weight heparin in plaster immobilization of the lower extremity]. / Ambulante Thromboseprophylaxe mit niedermolekularem Heparin bei Gipsimmobilisation der unteren Extremität.

Plaster cast immobilisation following trauma is a major risk factor for the development of deep vein thrombosis. In our controlled, randomized and prospective study on patients with minor injuries incidence of DVT in conservatively treated out-patients with plaster cast immobilisation of the leg was 3.9% in the control group (n = 126) without prophylaxis. By s.c. self-application of LMV heparin once daily the number of DVT in the prophylaxis group (n = 115) was reduced to 0. No severe side effects of NMH were observed. We conclude that thromboprophylaxis with LMW heparin once daily up to now conspiciously reduced the risk of DVT in outpatients with plaster cast immobilisation of the leg.

[Concept of functional therapy exemplified by fresh closed humeral fracture]. / Konzept der funktionellen Therapie am Beispiel des frischen geschlossenen Oberarmschaftbruches.

The method of functional treatment of closed humerus fractures has gained an established position of success. A good outcome has proved to depend not only on correct indication, but it also depends decisively on physiotherapeutic exercises. The challenge to the physiotherapist has grown, and a standardised concept is now required. The authors' own approach is described in some detail. Excellent success was obtained from 80 in 82 cases, with average periods of treatment being shortened by something between two and four weeks.

The influence of carotid body stimulation on oxygen tension and microcirculation of various organs of the cat.

To determine the importance of chemoreflex control for microcirculation, we investigated tissue pO2 and local flow on the surface of muscle, kidney, liver, and heart under systemic hypoxia and under isolated hypoxic perfusion of the carotid body in anaesthetized (pentobarbital) and artificially ventilated cats. Under systemic hypoxia, local blood flow mainly decreased in muscle and kidney, whereas liver and heart showed a flow distribution mainly with a flow decrease. Under systemic hypoxia, tissue pO2 decreased to values in the range of 0 to 10 Torr. A linear relationship was found between the pO2 change under hypoxia and the normoxic pO2 in the investigated organs, indicating local regulatory mechanisms of microcirculation. Isolated hypoxic perfusion of the carotid body caused a microflow increase in kidney in about 63%, in liver in about 55%, and in heart in all cases. Hypoxic perfusion of the carotid body caused pO2 increases in kidney and liver with mean pO2 values of 3 and 4 Torr, respectively, whereas, it produced no significant pO2 change in heart and muscle. The pO2 changes in kidney and liver significantly depended on the normoxic basic tissue pO2 level, indicating, in connection with local flow increases, a redistribution of local flow in these organs.