Jung’s Theorem Applied in Nuclear Track Methodology

Nuclear track density provides accelerator beam imaging and diagnostic employing CR-39 passive detectors. Counting charged particles related tracks by automated reading systems depend on the accuracy of microscope field view other that chemical etching procedure and frequency of overlapped tracks. The study, to propose a method to determined track density for analyser optical field view not calibrated. The approach Jungs’ theorem, provides the area value based on the maximum distance for two selected etched tracks. Results show that the new method has its importance when microscope field view calibration is not available with precision for accelerator beam diagnostics

The Role of Hydrogen Bonds in the Stabilization of Silver-Mediated Cytosine Tetramers

Peer reviewe

Production of Lipopeptides by Fermentation Processes: Endophytic Bacteria, Fermentation Strategies and Easy Methods for Bacterial Selection

Lipopeptides constitute an important class of microbial secondary metabolites. Some lipopeptides have potent therapeutic activities such as antibacterial, antiviral, antifungal, antitumor and immunomodulator. Surfactin, iturin, fengycin, lichenysin and bacillomycin D from Bacillus species, daptomycin from Streptomyces roseosporus and rhamnolipids from Pseudomonas aeruginosa are among the most studied lipopeptides. These molecules are good candidates to replace those antibiotics and antifungals with no effect on pathogenic microorganisms. Microbial lipopeptides are produced via fermentation processes by bacteria, yeast and actinomycetes either on water miscible and immiscible substrates. However, the major bottlenecks in lipopeptide production are yield increase and cost reduction. Improving the bioindustrial production processes relies on many issues such as selecting hyperproducing strains and the appropriate extraction techniques; purification and identification by Polymerase Chain Reaction(PCR), High Performance Liquid Chromatography-Mass Spectrometry(HPLC-MS), Matrix Assisted Laser Desorption Ionization-Time of Flight-Mass Spectrometry(MALDI-TOF-MS); the use of cheap raw materials and the optimization of medium-culture conditions. The purpose of this chapter is to orient the reader on the key elements in this field, including the selection of analytical strategies to get a good microbial strain as well as to show some examples of liquid and solid-state low-cost fermentation processes. Last, we introduce endophytic bacteria as lipopeptide-producer candidates

A cardinal role for cathepsin D in co-ordinating the host-mediated apoptosis of macrophages and killing of pneumococci

The bactericidal function of macrophages against pneumococci is enhanced by their apoptotic demise, which is controlled by the anti-apoptotic protein Mcl-1. Here, we show that lysosomal membrane permeabilization (LMP) and cytosolic translocation of activated cathepsin D occur prior to activation of a mitochondrial pathway of macrophage apoptosis. Pharmacological inhibition or knockout of cathepsin D during pneumococcal infection blocked macrophage apoptosis. As a result of cathepsin D activation, Mcl-1 interacted with its ubiquitin ligase Mule and expression declined. Inhibition of cathepsin D had no effect on early bacterial killing but inhibited the late phase of apoptosis-associated killing of pneumococci in vitro. Mice bearing a cathepsin D-/- hematopoietic system demonstrated reduced macrophage apoptosis in vivo, with decreased clearance of pneumococci and enhanced recruitment of neutrophils to control pulmonary infection. These findings establish an unexpected role for a cathepsin D-mediated lysosomal pathway of apoptosis in pulmonary host defense and underscore the importance of apoptosis-associated microbial killing to macrophage function

First-Line Ipatasertib, Atezolizumab, and Taxane Triplet for Metastatic Triple-Negative Breast Cancer: Clinical and Biomarker Results.

PURPOSE: To evaluate a triplet regimen combining immune checkpoint blockade, AKT pathway inhibition, and (nab-) paclitaxel as first-line therapy for locally advanced/metastatic triple-negative breast cancer (mTNBC). PATIENTS AND METHODS: The single-arm CO40151 phase Ib study (NCT03800836), the single-arm signal-seeking cohort of IPATunity130 (NCT03337724), and the randomized phase III IPATunity170 trial (NCT04177108) enrolled patients with previously untreated mTNBC. Triplet therapy comprised intravenous atezolizumab 840 mg (days 1 and 15), oral ipatasertib 400 mg/day (days 1-21), and intravenous paclitaxel 80 mg/m2 (or nab-paclitaxel 100 mg/m2; days 1, 8, and 15) every 28 days. Exploratory translational research aimed to elucidate mechanisms and molecular markers of sensitivity and resistance. RESULTS: Among 317 patients treated with the triplet, efficacy ranged across studies as follows: median progression-free survival (PFS) 5.4 to 7.4 months, objective response rate 44% to 63%, median duration of response 5.6 to 11.1 months, and median overall survival 15.7 to 28.3 months. The safety profile was consistent with the known toxicities of each agent. Grade ≥3 adverse events were more frequent with the triplet than with doublets or single-agent paclitaxel. Patients with PFS >10 months were characterized by NF1, CCND3, and PIK3CA alterations and increased immune pathway activity. PFS <5 months was associated with CDKN2A/CDKN2B/MTAP alterations and lower predicted phosphorylated AKT-S473 levels. CONCLUSIONS: In patients with mTNBC receiving an ipatasertib/atezolizumab/taxane triplet regimen, molecular characteristics may identify those with particularly favorable or unfavorable outcomes, potentially guiding future research efforts

Intake design for an Atmosphere-Breathing Electric Propulsion System (ABEP)

Challenging space missions include those at very low altitudes, where the atmosphere is source of aerodynamic drag on the spacecraft. To extend the lifetime of such missions, an efficient propulsion system is required. One solution is Atmosphere-Breathing Electric Propulsion (ABEP) that collects atmospheric particles to be used as propellant for an electric thruster. The system would minimize the requirement of limited propellant availability and can also be applied to any planetary body with atmosphere, enabling new missions at low altitude ranges for longer times. IRS is developing, within the H2020 DISCOVERER project, an intake and a thruster for an ABEP system. The article describes the design and simulation of the intake, optimized to feed the radio frequency (RF) Helicon-based plasma thruster developed at IRS. The article deals in particular with the design of intakes based on diffuse and specular reflecting materials, which are analysed by the PICLas DSMC-PIC tool. Orbital altitudes and the respective species based on the NRLMSISE-00 model (O, , , He, Ar, H, N) are investigated for several concepts based on fully diffuse and specular scattering, including hybrid designs. The major focus has been on the intake efficiency defined as , with the incoming particle flux, and the one collected by the intake. Finally, two concepts are selected and presented providing the best expected performance for the operation with the selected thruster. The first one is based on fully diffuse accommodation yielding to and the second one based on fully specular accommodation yielding to . Finally, also the influence of misalignment with the flow is analysed, highlighting a strong dependence of in the diffuse-based intake while, for the specular-based intake, this is much lower finally leading to a more resilient design while also relaxing requirements of pointing accuracy for the spacecraft

Intake Design for an Atmosphere-Breathing Electric Propulsion System (ABEP)

Challenging space missions include those at very low altitudes, where the atmosphere is source of aerodynamic drag on the spacecraft. To extend the lifetime of such missions, an efficient propulsion system is required. One solution is Atmosphere-Breathing Electric Propulsion (ABEP) that collects atmospheric particles to be used as propellant for an electric thruster. The system would minimize the requirement of limited propellant availability and can also be applied to any planetary body with atmosphere, enabling new missions at low altitude ranges for longer times. IRS is developing, within the H2020 DISCOVERER project, an intake and a thruster for an ABEP system. The article describes the design and simulation of the intake, optimized to feed the radio frequency (RF) Helicon-based plasma thruster developed at IRS. The article deals in particular with the design of intakes based on diffuse and specular reflecting materials, which are analysed by the PICLas DSMC-PIC tool. Orbital altitudes $h=150-250$ km and the respective species based on the NRLMSISE-00 model (O, $N_2$, $O_2$, He, Ar, H, N) are investigated for several concepts based on fully diffuse and specular scattering, including hybrid designs. The major focus has been on the intake efficiency defined as $\eta_c=\dot{N}_{out}/\dot{N}_{in}$, with $\dot{N}_{in}$ the incoming particle flux, and $\dot{N}_{out}$ the one collected by the intake. Finally, two concepts are selected and presented providing the best expected performance for the operation with the selected thruster. The first one is based on fully diffuse accommodation yielding to $\eta_c<0.46$ and the second one based un fully specular accommodation yielding to $\eta_c<0.94$. Finally, also the influence of misalignment with the flow is analysed, highlighting a strong dependence of $\eta_c$ in the diffuse-based intake while, ...Comment: Accepted Versio

Neuropsychiatric profiles and conversion to dementia in mild cognitive impairment, a latent class analysis

Altres ajuts: Fondo Europeo de Desarrollo Regional (FEDER)Altres ajuts: Generalitat de Catalunya. Programa CERCAAltres ajuts: Instituto de Salud Carlos III (CIBERSAM i CIBERNED)Altres ajuts: Fundació "La Caixa"Altres ajuts: Grífols SA (GR@ACE project)Neuropsychiatric symptoms (NPS) have been recently addressed as risk factors of conversion to Alzheimer's disease (AD) and other dementia types in patients diagnosed with Mild Cognitive Impairment (MCI). Our aim was to determine profiles based on the prominent NPS in MCI patients and to explore the predictive value of these profiles on conversion to specific types of dementia. A total of 2137 MCI patients monitored in a memory clinic were included in the study. Four NPS profiles emerged (classes), which were defined by preeminent symptoms: Irritability, Apathy, Anxiety/Depression and Asymptomatic. Irritability and Apathy were predictors of conversion to dementia (HR = 1.43 and 1.56, respectively). Anxiety/depression class showed no risk effect of conversion when compared to Asymptomatic class. Irritability class appeared as the most discriminant neuropsychiatric condition to identify non-AD converters (i.e., frontotemporal dementia, vascular dementia, Parkinson's disease and dementia with Lewy Bodies). The findings revealed that consistent subgroups of MCI patients could be identified among comorbid basal NPS. The preeminent NPS showed to behave differentially on conversion to dementia, beyond AD. Therefore, NPS should be used as early diagnosis facilitators, and should also guide clinicians to detect patients with different illness trajectories in the progression of MCI

Network meta‐analysis of post‐exposure prophylaxis randomized clinical trials

Objectives: We performed a network meta‐analysis of PEP randomized clinical trials to evaluate the best regimen. / Methods: After MEDLINE/Pubmed search, studies were included if: (1) were randomized, (2) comparing at least 2 PEP three‐drug regimens and, (3) reported completion rates or discontinuation at 28 days. Five studies with 1105 PEP initiations were included and compared ritonavir‐boosted lopinavir (LPV/r) vs. atazanavir (ATV) (one study), cobicistat‐boosted elvitegravir (EVG/c) (one study), raltegravir (RAL) (one study) or maraviroc (MVC) (two studies). We estimated the probability of each treatment of being the best based on the evaluation of five outcomes: PEP non‐completion at day 28, PEP discontinuation due to adverse events, PEP switching due to any cause, lost to follow‐up and adverse events. / Results: Participants were mostly men who have sex with men (n = 832, 75%) with non‐occupational exposure to HIV (89.86%). Four‐hundred fifty‐four (41%) participants failed to complete their PEP course for any reason. The Odds Ratio (OR) for PEP non‐completion at day 28 in each antiretroviral compared to LPV/r was: ATV 0.95 (95% CI 0.58–1.56; EVG/c: OR 0.65 95% CI 0.30–1.37; RAL: OR 0.68 95% CI 0.41–1.13; and MVC: OR 0.69 95% CI 0.47–1.01. In addition, the rankogram showed that EVG/c had the highest probability of being the best treatment for the lowest rates in PEP non‐completion at day 28, switching, lost to follow‐up or adverse events and MVC for PEP discontinuations due to adverse events. / Conclusions: Our study shows the advantages of integrase inhibitors when used as PEP, particularly EVG as a Single‐Tablet Regimen

MartiTracks: A Geometrical Approach for Identifying Geographical Patterns of Distribution

Panbiogeography represents an evolutionary approach to biogeography, using rational cost-efficient methods to reduce initial complexity to locality data, and depict general distribution patterns. However, few quantitative, and automated panbiogeographic methods exist. In this study, we propose a new algorithm, within a quantitative, geometrical framework, to perform panbiogeographical analyses as an alternative to more traditional methods. The algorithm first calculates a minimum spanning tree, an individual track for each species in a panbiogeographic context. Then the spatial congruence among segments of the minimum spanning trees is calculated using five congruence parameters, producing a general distribution pattern. In addition, the algorithm removes the ambiguity, and subjectivity often present in a manual panbiogeographic analysis. Results from two empirical examples using 61 species of the genus Bomarea (2340 records), and 1031 genera of both plants and animals (100118 records) distributed across the Northern Andes, demonstrated that a geometrical approach to panbiogeography is a feasible quantitative method to determine general distribution patterns for taxa, reducing complexity, and the time needed for managing large data sets