Interference of Mycobacterium tuberculosis with macrophage responses

Tuberculosis, caused by Mycobacterium tuberculosis, has become an important health and economic burden, with more than four thousand people succumbing to the disease every day. Thus, there is an urgent need to understand the molecular basis of this pathogen's success in causing disease in humans, in order to develop new drugs superior to conventional drugs available at present. One reason why M. tuberculosis is such a dangerous microbe lies within its ability to survive within infected hosts, thereby efficiently circumventing host immune responses. Over the past few years, a number of mechanisms have been unravelled that are utilized by M. tuberculosis to survive within hosts and to avoid immune defence mechanisms. Several of these mechanisms have been described in this communication that may be useful for the development of novel compounds to treat tuberculosis

Exploring prospects of novel drugs for tuberculosis

Tuberculosis remains a disease with an enormous impact on public health worldwide. With the continuously increasing epidemic of drug-resistant tuberculosis, new drugs are desperately needed. However, even for the treatment of drug-sensitive tuberculosis, new drugs are required to shorten the treatment duration and thereby prevent development of drug resistance. Within the past ten years, major advances in tuberculosis drug research have been made, leading to a considerable number of antimycobacterial compounds which are now in the pipeline. Here we discuss a number of these novel promising tuberculosis drugs, as well as the discovery of two new potential drug targets for the development of novel effective drugs to curb the tuberculosis pandemic, ie, the coronin 1 and protein kinase G pathways. Protein kinase G is secreted by mycobacteria and is responsible for blocking lysosomal delivery within the macrophage. Coronin 1 is responsible for activating the phosphatase, calcineurin, and thereby preventing phagosome-lysosome fusion within the macrophage. Blocking these two pathways may lead to rapid killing of mycobacteri

Instructing Hierarchical Tasks to Robots by Verbal Commands

Natural language is an effective tool for communication, as information can be expressed in different ways and at different levels of complexity. Verbal commands, utilized for instructing robot tasks, can therefor replace traditional robot programming techniques, and provide a more expressive means to assign actions and enable collaboration. However, the challenge of utilizing speech for robot programming is how actions and targets can be grounded to physical entities in the world. In addition, to be time-efficient, a balance needs to be found between fine- and course-grained commands and natural language phrases. In this work we provide a framework for instructing tasks to robots by verbal commands. The framework includes functionalities for single commands to actions and targets, as well as longer-term sequences of actions, thereby providing a hierarchical structure to the robot tasks. Experimental evaluation demonstrates the functionalities of the framework by human collaboration with a robot in different tasks, with different levels of complexity. The tools are provided open-source at https://petim44.github.io/voice-jogger/Comment: 7 pages, accepted to 16th IEEE/SICE International Symposium on System Integratio

A history of transurethral resection of the prostate should not be a contra-indication for low-dose-rate 125I prostate brachytherapy: results of a prospective Uro-GEC phase-II trial

Purpose Early reports suggested that transurethral resection (TURP) prior to permanent seed brachytherapy (BT) results in high incontinence rates. Guidelines consider prior TURP as a contra-indication to treatment, but improvements in imaging and treatment planning may reduce this risk, and are investigated in this prospective study. Material and methods 99 men with histologically proven low- to intermediate-risk, localized prostate cancer, with a history of TURP performed at least 3 months before BT procedure were enrolled. All patients received a permanent seed implant between March 2009 and June 2015. Intra-operative interactive planning was recommended to ensure optimal accuracy of seed placement during the procedure. No supplemental external beam was allowed. Target and organ at risk contouring, definition of clinical target volume (CTV), and dosimetric parameters followed the modified GEC-ESTRO guidelines for permanent seed implants, as described an earlier report of our group. Follow-up was scheduled every 3 months for the first year, and every 6 months afterwards, with minimum follow-up of 2 years. Study endpoints the primary endpoint was the incidence of post-implant urinary incontinence. Secondary endpoints were the incidence of urinary and gastro-intestinal toxicity, the eventual impact on the sexual function, and the freedom from biochemical failure. Results The median follow-up time for these 99 patients was 49 months (min. 24, max. 96). In this series, the incontinence rate was 2% after TURP + BT and 2% in case of TURP + BT + re-TURP, ending up with a total urinary incontinence rate of 4%. Acute and late urinary toxicities were extremely low. No significant late gastro-intestinal toxicity was seen, and the 5-year biochemical non-evidence of disease (bNED) was 93%. Conclusions The excellent long-term results and low morbidity presented as well as many advantages of prostate brachytherapy over other treatments demonstrates that brachytherapy is an effective treatment for patients with transurethral resection and organ-confined prostate cancer

Assessing the Sensitivity and Uncertainty of an NH3 Emission Reduction Calculator for Dairy Cattle Barns by Means of Monte Carlo Analysis Combined with Least Square Linearization

With regard to Natura 2000, the Flemish government (Belgium) established the Programmatic Approach to Nitrogen (PAS: acronym in Flemish), with the aim of reducing environmental overload of nitrogen compounds. This approach will have substantial consequences for livestock farms located next to or within special areas of conservation and will likely result in generic measures to reduce ammonia (NH3) emissions from livestock facilities. An NH3 emission reduction calculator for dairy cattle systems (AEREC-DC) was adapted based on a mechanistic approach. Reduction coefficients estimated with this tool are used to assess the efficiency of “low NH3 emission” techniques which can be implemented in Flanders at a later stage. Field measurements will be made in the future to confirm/correct them. Emission reduction techniques combining processes such as floor scraping, flushing, manure acidification, and different types of floor were modeled. The tool comprises 36 input variables, some of which have values that are based on experimental measurements. Nevertheless, reliable information concerning other relevant variables are scarce in the literature. Hence, model sensitivity analysis is imperative. We hypothesize that the ranking of input variables in terms of their effect on the model outcome will change if different uncertainty ranges are assigned to them. Hence, this study was conducted to combine Monte Carlo Analysis associated with Least Square Linearization in order to perform sensitivity and uncertainty analyses on AEREC-DC. The sensitivity analysis was performed by assigning each input variables’ probability distribution function (PDF) with a relatively narrow variance (1% of mean value). The uncertainty analysis was carried out by gradually increasing the PDF’s variance up to what is considered realistic. The outcomes of this study will help deciding which variables urgently need to be monitored experimentally in order to improve predictions’ accuracy