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Emerging evidence points to an unexpected diversification of core promoter recognition complexes that serve as important regulators of cell-type specific gene transcription. Here, we report that the orphan TBP-associated factor TAF9B is selectively up-regulated upon in vitro motor neuron differentiation, and is required for the transcriptional induction of specific neuronal genes, while dispensable for global gene expression in murine ES cells. TAF9B binds to both promoters and distal enhancers of neuronal genes, partially co-localizing at binding sites of OLIG2, a key activator of motor neuron differentiation. Surprisingly, in this neuronal context TAF9B becomes preferentially associated with PCAF rather than the canonical TFIID complex. Analysis of dissected spinal column from Taf9b KO mice confirmed that TAF9B also regulates neuronal gene transcription in vivo. Our findings suggest that alternative core promoter complexes may provide a key mechanism to lock in and maintain specific transcriptional programs in terminally differentiated cell types.DOI: http://dx.doi.org/10.7554/eLife.02559.001.

SUMMARY The great concern about climate change and fossil fuel dependency is strongly encouraging the development and use of electric vehicles. However, the wide adoption of such vehicles is not possible without the deployment of charging infrastructures capable of integrating them into current and future electricity grids. There are many on-going research efforts and even products that propose different solutions to this problem. Standing out among them is the Spanish research project DOMOCELL, which aims at designing and developing a smart charging infrastructure for private parking lots. In this paper, we present its communications architecture, designed under the guidelines of efficiency, reliability, and scalability. In addition, we describe, supported by some practical use cases and emulations, how user authentication and authorization, as well as accounting and billing of power consumption, are performed even in roaming scenarios. Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Nowadays society is demanding more and more smart healthcare services that allow monitoring patient status in a non-invasive way, anywhere and anytime. Thus, healthcare applications are currently facing important challenges guided by the u-health (ubiquitous health) and p-health (pervasive health) paradigms. New emerging technologies can be combined with other widely deployed ones to develop such next-generation healthcare systems. The main objective of this paper is to review and provide more details on the work presented in "LOBIN: E-Textile and Wireless-Sensor-Network-Based Platform for Healthcare Monitoring in Future Hospital Environments", published in the IEEE Transactions on Information Technology in Biomedicine, as well as to extend and update the comparison with other similar systems. As a result, the paper discusses the main advantages and disadvantages of using different architectures and communications technologies to develop wearable systems for pervasive healthcare applications. [ABSTRACT FROM AUTHOR]

The Interactive Module for Cavity Navigation (IMCA) was created in order to enhance the Web Environment for Surgical Skills Training in Otolaryngology (WESST – OT); later, it was found that it could be used as an independent module which allowed the practice of path navigation in any medical cavity, and its potential use with patients was evidenced. This paper describes the making of IMCA and the potential use of genetic algorithms in path generation. [ABSTRACT FROM AUTHOR]

The development of TGFβR inhibitors (TGFβRi) as new medicines have been affected by cardiac valvulopathy and arteriopathy toxicity findings in nonclinical toxicology studies. PF-06952229 (MDV6058) selected using rational drug design is a potent and selective TGFβRI inhibitor (TGFβRIi) with a relatively clean off-target selectivity profile and good pharmacokinetic properties across species. PF-06952229 inhibited clinically translatable phospho-SMAD2 biomarker ({greater than or equal to}60%) in human and cynomolgus monkey peripheral blood mononuclear cells, as well as in mouse and rat splenocytes. Using an optimized, intermittent dosing schedule (7 day-on, 7-off/cycle; five cycles), PF-06952229 demonstrated efficacy in a 63-day syngeneic MC38 colon carcinoma mouse model. In the pivotal repeat dose toxicity studies (rat and cynomolgus monkey), PF-06952229 on an intermittent dosing schedule (5 day-on, 5-off/cycle; five cycles, 28 doses) showed no cardiac-related adverse findings. However, new toxicity findings related to PF-06952229 included reversible hepatocellular (hepatocyte necrosis with corresponding clinically monitorable transaminase increases) and lung (hemorrhage with mixed cell inflammation) findings at {greater than or equal to} targeted projected clinical efficacious exposures. Furthermore, partially reversible cartilage hypertrophy (trachea and femur in rat; femur in monkey), and partially to fully reversible, clinically monitorable decreases in serum phosphorus and urinary phosphate, at {greater than or equal to} projected clinically efficacious exposures were observed. Given the integral role of TGFβ in endochondral bone formation, cartilage findings in toxicity studies have been observed with other TGFβRi class of compounds. The favorable cumulative profile of PF-06952229 in biochemical, pharmacodynamic, pharmacokinetic and nonclinical studies, allowed for its evaluation in cancer patients using the intermittent dosing schedule (7-on/7-off) and careful protocol-defined monitoring. Significance Statement Only a few TGFβRi have progressed for clinical evaluation due to adverse cardiac findings in pivotal nonclinical toxicity studies. Potential translation of such findings in patients are of major concern. Using a carefully optimized intermittent dosing schedule PF-06952229 has demonstrated impressive pharmacological efficacy in the syngeneic MC38 colon carcinoma mouse model. Additionally, a nonclinical toxicology package without cardiovascular liabilities and generally monitorable toxicity profile has been completed. The compound presents an acceptable ICHS9 compliant profile for the intended-to-treat cancer patients.

Objective: To assess current management of renal cell carcinoma (RCC) extending into the inferior vena cava (IVC): staging, diagnosis, surgical approach, adjuvant therapy, prognostic factors and survival rate., Materials and Methods: Nineteen cases of RCC extending into the IVC undergoing surgical resection from January 1988 to August 2008 were reviewed. TNM staging and Neves-Zincke grading of the tumor were also assessed. Surgical approach depended on thrombus level., Results: With a perioperative mortality rate of 10.5% and a mean follow-up of 22.65 months (range 2-79), 5 patients are still alive, while 11 patients died from the disease, 1 from an unrelated cause, and 2 were lost to follow-up. Patients with metastatic disease received adjuvant treatment with immunotherapy or kinase inhibitors. Mean survival was 15.1 months. Significant differences were found in 3- and 5-year survival rates in patients staged as N0M0 as compared to all other stages (N+M0, N0M+, N+M+). No differences were found depending on thrombus level., Conclusions: RCC with thrombus in the IVC is a tumor with a high mortality rate. Surgery continues to be the best option, and requires adequate preoperative evaluation and the support of an experienced and well trained multidisciplinary team. Survival depends on disease extension.

The Interactive Module for Cavity Navigation (IMCA) was created in order to enhance the Web Environment for Surgical Skills Training in Otolaryngology (WESST--OT); later, it was found that it could be used as an independent module which allowed the practice of path navigation in any medical cavity, and its potential use with patients was evidenced. This paper describes the making of IMCA and the potential use of genetic algorithms in path generation.

Objective: To determine the therapeutic efficacy and safety of a nitric oxide (NO) isosorbide dinitrate donor to induce cervical ripening of women with missed abortions before surgical evacuation of the uterus., Design: A prospective, randomised, double-blind controlled trial., Setting: Tertiary referral maternity teaching hospital. Population Sixty women with missed abortions and no cervical dilation., Methods: Women requesting surgical evacuation of the uterus were randomly selected to receive endocervical 80 mg/1.5 mL isosorbide dinitrate gel solution (n= 30) or 400 mug/1.5 mL misoprostol gel solution (n= 30) every 3 hours to a maximum of four doses or until reaching cervical ripening. Vital signs and symptoms were recorded at baseline and then every 3 hours until finishing therapy. Adverse events, such as headache, abdominal pain, pelvic pain, backache, nausea and vomiting, were evaluated., Main Outcome Measures: Probability of reaching cervical ripening >8 mm Hegar dilator; evaluated at 3, 6, 9 and 12 hours after application of isosorbide dinitrate or misoprostol., Results: The probabilities of induction of cervical ripening by isosorbide dinitrate and misoprostol after four repeated doses at 3-hour intervals were significantly different (P<0.001). Efficacy of therapy after 12 hours was 97% for the isosorbide dinitrate group and 70% for the misoprostol group. Systolic and diastolic blood pressures were lower after administration of isosorbide dinitrate than prostaglandin analogues. The difference in the mean systolic and diastolic blood pressure between treatment groups was greatest at 3 hours, with a difference of 7.7 mmHg (P<0.001) and 5.9 mmHg (P<0.003), respectively. The most frequent side effect associated with isosorbide dinitrate administration was headache, which occurred in 18 out of 30 patients, compared with only 5 out of 30 women in the misoprostol group [relative risk (RR) 2.41, 95% confidence interval (CI) 1.45-4.03, P<0.001). Women treated with misoprostol reported mainly pelvic pain (RR 3.24, 95% CI 1.99-5.27, P<0.001)., Conclusions: Intracervical administration of 80 mg isosorbide dinitrate in women with missed abortions appears to be effective for cervical ripening prior to surgical evacuation of the uterus. Differences in the incidence of non-serious adverse events are not likely to be clinically significant.