Effect of treatment with 13-cis-retinoic acid and ara-C on the hematopoietic stem cells of patients with myelodysplastic syndromes

PURPOSE: To assess the "in vivo" effect of 13-cis-retinoic acid and low dose Ara-C in MDS as well as to establish "in vitro" advantage of retinoid dose-related growth pattern on bone marrow cultures as defined by culture timing and CFU-GM proliferative response. PATIENTS AND METHODS: We evaluated 28 patients diagnosed of MDS according to FAB classification, of whom 4 cases had RA, 8 cases SRA, 14 cases RAEB and 2 cases RAEB-T. Patients who had RA and SRA were treated with oral 13-cis-retinoic acid at doses of 20-40 mg daily for 4 months and those cases with RAEB and RAEB-T had subcutaneous Ara-C at doses of 3 mg/m2 twice a day for 21 days. The "in vivo" and "in vitro" effect of retinoic acid on the haemopoietic differentiation was evaluated by the growth CFU-GM in semisolid cell culture methods. RESULTS: Increasing in vitro concentrations of 13-cis retinoic acid did not enhance the growth of myelodysplastic progenitors. Nevertheless, our study did not find any beneficial therapeutic effect of retinoic compounds in MDS patients. In this study, low-dose Ara-C (3 mg/m2) showed similar effects when compared with higher doses reported by others. Furthermore, in terms of CFU-GM proliferation the concentration of colonies before and after treatment were fairly similar in all but two patients. CONCLUSIONS: The results drawn from our study demonstrated that there is no beneficial advantage of 13-cis-retinoic acid as a differentiation inducing agent on myelodysplastic patients. In contrast, lower doses of Ara-C showed similar effects on haemopoiesis of MDS patients than standard doses of 10-20 mg/m2 but with less side effects.     

Experience report on the application of genetic algorithms to reduce costs of the software validation process in the automotive sector during an engine control unit project

Software Quality Journal - The number of electronic control units (ECU) installed in vehicles is increasingly high. Manufacturers must improve the software quality and reduce cost by proposing...     

Experimental modelling of free-surface dry granular flows under a centrifugal acceleration field

We investigate the dynamics of granular flows under the action of a centrifugal acceleration field. The granular flows consist of a monodisperse set of glass beads flowing down an inclined plane. The experiments are performed at variable slope angles \(\zeta \) and equivalent centrifugal accelerations \(a_\text {cf}\equiv Ng\). We study the effect of this parameters on the superficial flow velocity u and flow height h. Two trends are observed, by increasing \(\zeta \) and \(a_\text {cf}\), u increases proportionally, and h decreases asymptotically until a constant height. This relation is analysed in terms of the system potential and kinetic energy, leading to the estimation of equivalent impact forces one order of magnitude larger than those observed in small scale 1g laboratory experiments, with the possibility to reach higher forces by increasing N. Finally, considering the trend of u and h, our results suggest a scaling principle of inertial velocity proportional to \(\sqrt{N}\).     

Bandwidth selection in kernel density estimation for interval-grouped data

When interval-grouped data are available, the classical Parzen–Rosenblatt kernel density estimator has to be modified to get a computable and useful approach in this context. The new nonparametric grouped data estimator needs of the choice of a smoothing parameter. In this paper, two different bandwidth selectors for this estimator are analyzed. A plug-in bandwidth selector is proposed and its relative rate of convergence obtained. Additionally, a bootstrap algorithm to select the bandwidth in this framework is designed. This method is easy to implement and does not require Monte Carlo. Both proposals are compared through simulations in different scenarios. It is observed that when the sample size is medium or large and grouping is not heavy, both bandwidth selection methods have a similar and good performance. However, when the sample size is large and under heavy grouping scenarios, the bootstrap bandwidth selector leads to better results.     

Colloidal Quantum Dot Infrared Lasers Featuring Sub-Single-Exciton Threshold and Very High Gain

The use of colloidal quantum dots (CQDs) as a gain medium in infrared laser devices has been underpinned by the need for high pumping intensities, very short gain lifetimes, and low gain coefficients. Here, PbS/PbSSe core/alloyed-shell CQDs are employed as an infrared gain medium that results in highly suppressed Auger recombination with a lifetime of 485 ps, lowering the amplified spontaneous emission (ASE) threshold down to 300 µJ cm⁻², and showing a record high net modal gain coefficient of 2180 cm⁻¹. By doping these engineered core/shell CQDs up to nearly filling the first excited state, a significant reduction of optical gain threshold is demonstrated, measured by transient absorption, to an average-exciton population-per-dot 〈N^th〉_g of 0.45 due to bleaching of the ground state absorption. This in turn have led to a fivefold reduction in ASE threshold at 〈N^th〉_ASE = 0.70 excitons-per-dot, associated with a gain lifetime of 280 ps. Finally, these heterostructured QDs are used to achieve near-infrared lasing at 1670 nm at a pump fluences corresponding to sub-single-exciton-per-dot threshold (〈N^th〉_Las = 0.87). This work brings infrared CQD lasing thresholds on par to their visible counterparts, and paves the way toward solution-processed infrared laser diodes.     

An internet of things–based personal device for diabetes therapy management in ambient assisted living (AAL)

Diabetes therapy management in AAL environments, such as old people and diabetes patients homes, is a very difficult task since many factors affect a patient’s blood sugar levels. Factors such as illness, treatments, physical and psychological stress, physical activity, drugs, intravenous fluids and change in the meal plan cause unpredictable and potentially dangerous fluctuations in blood sugar levels. Right now, operations related to dosage are based on insulin infusion protocol boards, which are provided by physicians to the patients. These boards are not considering very influential factors such as glycemic index from the diet, consequently patients need to estimate the dosage leading to dose error, which culminates in hyperglycemia and hypoglycemia episode. Therefore, right insulin infusion calculation needs to be supported by the next generation of personal-care devices. For this reason, a personal device has been developed to assist and consider more factors in the insulin therapy dosage calculation. The proposed solution is based on Internet of things in order to, on the one hand, support a patient’s profile management architecture based on personal RFID cards and, on the other hand, provide global connectivity between the developed patient’s personal device based on 6LoWPAN, nurses/physicians desktop application to manage personal health cards, glycemic index information system, and patient’s web portal. This solution has been evaluated by a multidisciplinary group formed by patients, physicians, and nurses.     

Development of an automated platform for high-throughput P1-phage transduction of Escherichia coli

Synthetic biology depends on the ability to rapidly produce strains with improved phenotypes but is limited by the ability to rapidly produce strain collections with directed mutations. Here, we present a system capable of overcoming this limitation through automated P1-phage transductions of Escherichia coli. By combining the Keio collection of single-gene deletion E. coli mutants with P1-phage, it is possible to generate an engineered host-strain collection consisting of every possible gene deletion mutant. This strategy was tested by transducing 355 genetic markers from the Keio collection into five different host strains, and it achieved a 98% success rate. This method offers an improved mechanism for rapidly engineering collections of microbes and provides one method for rapidly deploying a broader synthetic biology effort.