Oncogenic Gain of Function in Glioblastoma Is Linked to Mutant p53 Amyloid Oligomers.

Tumor-associated p53 mutations endow cells with malignant phenotypes, including chemoresistance. Amyloid-like oligomers of mutant p53 transform this tumor suppressor into an oncogene. However, the composition and distribution of mutant p53 oligomers are unknown and the mechanism involved in the conversion is sparse. Here, we report accumulation of a p53 mutant within amyloid-like p53 oligomers in glioblastoma-derived cells presenting a chemoresistant gain-of-function phenotype. Statistical analysis from fluorescence fluctuation spectroscopy, pressure-induced measurements, and thioflavin T kinetics demonstrates the distribution of oligomers larger than the active tetrameric form of p53 in the nuclei of living cells and the destabilization of native-drifted p53 species that become amyloid. Collectively, these results provide insights into the role of amyloid-like mutant p53 oligomers in the chemoresistance phenotype of malignant and invasive brain tumors and shed light on therapeutic options to avert cancer

Non-Destructive Testing Inspection for Metal Components Produced Using Wire and Arc Additive Manufacturing

Funding Information: JPO acknowledges funding by national funds from FCT—Fundação para a Ciência e a Tecnologia, I.P., in the scope of the projects LA/P/0037/2020. This activity has received funding from the European Institute of Innovation and Technology (EIT)—Project Smart WAAM: Microstructural Engineering and Integrated Non-Destructive Testing. This body of the European Union receives support from the European Union’s Horizon 2020 research and innovation programme. Publisher Copyright: © 2023 by the authors.The wire and arc additive manufacturing (WAAM) process enables the creation and repair of complex structures based on the successive deposition of fed metal in the form of a wire that is fused with an electric arc and then solidifies. The high number of depositions required to create or repair parts increases the likelihood of defect formation. If these are reliably detected during manufacturing, timely correction is possible. However, high temperatures and surface irregularity make inspection difficult. Furthermore, depending on the size, morphology, and location of the defect, the part can be rejected. Recent studies have shown that non-destructive testing (NDT) based on different physical phenomena for the timely, reliable, and customized detection of defects can significantly reduce the rejection rate and allow in-line repair, which consequently reduces waste and rework. This paper presents the latest developments in NDT for WAAM and its limitations and potential.publishersversionpublishe

Application of remote sensing to the study of the pelagic spiny lobster larval transport in the Tropical Atlantic

A conectividade de populações marinhas através da dispersão larval é crucial para a manutenção da produção pesqueira e da biodiversidade. A dispersão de larvas ocorre em diferentes escalas espaciais e temporais, de forma que o recobrimento global e escala sinóptica fazem dos dados de satélite ferramentas importantes para esses estudos. O objetivo deste artigo é apresentar os resultados do uso de dados de correntes geostróficas derivadas de satélites altímetros para simular o transporte de larvas de lagosta espinhosa no oceano Atlântico Tropical. As simulações foram realizadas ao longo do Atlântico Tropical (20ºN - 15ºS), iniciando em quatro locais (Cabo Verde, Costa do Marfim, Ilha de Ascensão e Arquipélago de Fernando de Noronha). Foi utilizado um modelo advectivo/difusivo forçado com o campo médio de circulação geostrófica calculado entre 2001 e 2005 e outro forçado com campo correspondente ao evento de El Niño 2002/2003. Os resultados obtidos sugerem que há uma intensificação de processos oceânicos de meso-escala durante o ano de El Niño, que promove a conectividade entre diferentes estoques e aumenta as chances de ocorrer um fluxo genético. Os dados de correntes geostróficas gerados a partir de satélites altímetros incorporados a um modelo advectivo/difusivo simples podem prover informações importantes acerca da dinâmica física necessárias para conduzir estudos sobre dispersão larval.The connectivity of marine populations via larval dispersal is crucial for the maintenance of fisheries production and biodiversity. Because larval dispersion takes place on different spatial scales, global operational satellite data can be successfully used to investigate the connectivity of marine populations on different spatial and temporal scales. In fact, satellite data have long been used for the study of the large and mesoscale biological processes associated with ocean dynamics. This paper presents simulations of spiny lobster larvae transport in the Tropical Atlantic using the geostrophic currents, generated by altimetry that feeds an advection/diffusion model. Simulations were conducted over the Tropical Atlantic (20ºN to 15ºS), considering four larvae release areas: the Cape Verde Archipelago, the Ivory Coast, Ascension Island and Fernando de Noronha Archipelago. We used mean geostrophic current (MGC) calculated from 2001 to 2005 to represent the mean circulation of the Tropical Atlantic. We also ran the model for the El Niño geostrophic current regime (ENGC) using part of the MGC data, representing the El Niño 2002/2003 event. Results suggest that the intensification of the mesoscale ocean processes associated with El Niño events promotes the connectivity between populations, increasing the chances of a genetic flux among different stocks. We concluded that the altimetry geostrophic current data together with a relatively simple advection/diffusion model can provide useful information about the physical dynamics necessary to conduct studies on larval dispersion

The Virtues of Frugality - Why cosmological observers should release their data slowly

Cosmologists will soon be in a unique position. Observational noise will gradually be replaced by cosmic variance as the dominant source of uncertainty in an increasing number of observations. We reflect on the ramifications for the discovery and verification of new models. If there are features in the full data set that call for a new model, there will be no subsequent observations to test that model's predictions. We give specific examples of the problem by discussing the pitfalls of model discovery by prior adjustment in the context of dark energy models and inflationary theories. We show how the gradual release of data can mitigate this difficulty, allowing anomalies to be identified, and new models to be proposed and tested. We advocate that observers plan for the frugal release of data from future cosmic variance limited observations.Comment: 5 pages, expanded discussion of Lambda and of blind anlysis, added refs. Matches version to appear in MNRAS Letter

A New Spin on Galactic Dust

We present a new puzzle involving Galactic microwave emission and attempt to resolve it. On one hand, a cross-correlation analysis of the WHAM H-alpha map with the Tenerife 10 and 15 GHz maps shows that the well-known DIRBE correlated microwave emission cannot be dominated by free-free emission. On the other hand, recent high resolution observations in the 8-10 GHz range with the Green Bank 140 ft telescope by Finkbeiner et al. failed to find the corresponding 8 sigma signal that would be expected in the simplest spinning dust models. So what physical mechanism is causing this ubiquitous dust-correlated emission? We argue for a model predicting that spinning dust is the culprit after all, but that the corresponding small grains are well correlated with the larger grains seen at 100 micron only on large angular scales. In support of this grain segregation model, we find the best spinning dust template to involve higher frequency maps in the range 12-60 micron, where emission from transiently heated small grains is important. Upcoming CMB experiments such as ground-based interferometers, MAP and Planck LFI with high resolution at low frequencies should allow a definitive test of this model.Comment: Minor revisions to match accepted ApJ version. 6 pages, 4 figs. Color figures and more foreground information at http://www.hep.upenn.edu/~angelica/foreground.html#spin or from [email protected]

The GMRT EoR Experiment: Limits on Polarized Sky Brightness at 150 MHz

The GMRT reionization effort aims to map out the large scale structure of the Universe during the epoch of reionization (EoR). Removal of polarized Galactic emission is a difficult part of any 21 cm EoR program, and we present new upper limits to diffuse polarized foregrounds at 150 MHz. We find no high significance evidence of polarized emission in our observed field at mid galactic latitude (J2000 08h26m+26). We find an upper limit on the 2-dimensional angular power spectrum of diffuse polarized foregrounds of [l^2 C_l/(2 PI)]^{1/2}< 3K in frequency bins of width 1 MHz at 300<l<1000. The 3-dimensional power spectrum of polarized emission, which is most directly relevant to EoR observations, is [k^3 P_p(k)/(2 PI^2)]^{1/2} 0.03 h/Mpc, k < 0.1 h/Mpc. This can be compared to the expected EoR signal in total intensity of [k^3 P(k)/ (2 PI^2) ]^{1/2} ~ 10 mK. We find polarized structure is substantially weaker than suggested by extrapolation from higher frequency observations, so the new low upper limits reported here reduce the anticipated impact of these foregrounds on EoR experiments. We discuss Faraday beam and depth depolarization models and compare predictions of these models to our data. We report on a new technique for polarization calibration using pulsars, as well as a new technique to remove broadband radio frequency interference. Our data indicate that, on the edges of the main beam at GMRT, polarization squint creates ~ 3% leakage of unpolarized power into polarized maps at zero rotation measure. Ionospheric rotation was largely stable during these solar minimum night time observations.Comment: 17 pages, 6 figures, 2 tables; changed figures, added appendices. To appear in MNRA

Quality Assessment of Photoplethysmography Signals For Cardiovascular Biomarkers Monitoring Using Wearable Devices

Photoplethysmography (PPG) is a non-invasive technology that measures changes in blood volume in the microvascular bed of tissue. It is commonly used in medical devices such as pulse oximeters and wrist worn heart rate monitors to monitor cardiovascular hemodynamics. PPG allows for the assessment of parameters (e.g., heart rate, pulse waveform, and peripheral perfusion) that can indicate conditions such as vasoconstriction or vasodilation, and provides information about microvascular blood flow, making it a valuable tool for monitoring cardiovascular health. However, PPG is subject to a number of sources of variations that can impact its accuracy and reliability, especially when using a wearable device for continuous monitoring, such as motion artifacts, skin pigmentation, and vasomotion. In this study, we extracted 27 statistical features from the PPG signal for training machine-learning models based on gradient boosting (XGBoost and CatBoost) and Random Forest (RF) algorithms to assess quality of PPG signals that were labeled as good or poor quality. We used the PPG time series from a publicly available dataset and evaluated the algorithm s performance using Sensitivity (Se), Positive Predicted Value (PPV), and F1-score (F1) metrics. Our model achieved Se, PPV, and F1-score of 94.4, 95.6, and 95.0 for XGBoost, 94.7, 95.9, and 95.3 for CatBoost, and 93.7, 91.3 and 92.5 for RF, respectively. Our findings are comparable to state-of-the-art reported in the literature but using a much simpler model, indicating that ML models are promising for developing remote, non-invasive, and continuous measurement devices.Comment: 9 page

Inhibitory action of Lippia gracilis Schauer essential oil on pathogenic bacteria and its effects as a growth promoter on quail

Aim of the study: To examine the in vitro sensitivity of Salmonella sp. and Escherichia coli strains to the microbial activity of Lippia gracilis Schauer essential oil (LGSEO) and to determine the optimal level of LGSEO as a growth promoter in diets for Japanese quail up to 35 days of age.Area of study: São Cristovão, Sergipe, Brazil.Material and methods: A total of 504 female Japanese quails (Coturnix coturnix japonica) at an initial average body weights of 6.80±0.10 g was allotted to one of six treatments (0, 100, 200, 300, 400 mg/kg of LGSEO and a diet containing 500 mg/kg of bacitracin methylene disalicylate) in 7 replicates, using 12 birds per experimental unit.Main results: In the age period of 21 to 35 days, feed intake declined linearly (p=0.04) and feed efficiency improved (p&lt;0.01), whereas no changes were observed in production performance (p&gt;0.05). The estimated (p=0.01) maximum relative weights of proventriculus and pancreas were obtained at the LGSEO inclusion levels of 196.5 and 251 mg/kg, respectively. Inclusion of 100 to 300 mg/kg of LGSEO in the diet reduced the total Salmonella sp. bacterial count.Research highlights: The use of 196.5 mg/kg of LGSEO in the diet of Japanese quail improved production performance and organ development and demonstrated potential antimicrobial capacity against Salmonella sp. bacteria. Due its pharmacological composition, LGSEO can potentially substitute to antimicrobials, because contains thymol and carvacrol as main active constituents

HIV-1/HSV-2 Co-Infected Adults in Early HIV-1 Infection Have Elevated CD4+ T Cell Counts

Introduction. HIV-1 is often acquired in the presence of pre-existing co-infections, such as Herpes Simplex Virus 2 (HSV-2). We examined the impact of HSV-2 status at the time of HIV-1 acquisition for its impact on subsequent clinical course, and total CD4+ T cell phenotypes. Methods. We assessed the relationship of HSV-1/HSV-2 co-infection status on CD4+ T cell counts and HIV-1 RNA levels over time prior in a cohort of 186 treatment naive adults identified during early HIV-1 infection. We assessed the activation and differentiation state of total CD4+ T cells at study entry by HSV-2 status. Results. of 186 recently HIV-1 infected persons, 101 (54%) were sero-positive for HSV-2. There was no difference in initial CD8+ T cell count, or differences between the groups for age, gender, or race based on HSV-2 status. Persons with HIV-1/HSV-2 co-infection sustained higher CD4+ T cell counts over time (+69 cells/ul greater (SD = 33.7, p = 0.04) than those with HIV-1 infection alone (Figure 1), after adjustment for HIV-1 RNA levels (-57 cells per 1 log(10) higher HIV-1 RNA, p<0.0001). We did not observe a relationship between HSV-2 infection status with plasma HIV-1 RNA levels over time. HSV-2 acquistion after HIV-1 acquisition had no impact on CD4+ count or viral load. We did not detect differences in CD4+ T cell activation or differentiation state by HSV-2+ status. Discussion. We observed no effect of HSV-2 status on viral load. However, we did observe that treatment naive, recently HIV-1 infected adults co-infected with HSV-2+ at the time of HIV-1 acquisition had higher CD4+ T cell counts over time. If verified in other cohorts, this result poses a striking paradox, and its public health implications are not immediately clear.Brazilian Program for STD and AIDS, Ministry of HealthSão Paulo City Health DepartmentFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)NIAID/NIHJohn E. Fogarty International CenterAIDS Research Institute of the AIDS Biology Program at UCSFCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Brazilian Ministry of EducationUniversidade Federal de São Paulo, Div Infect Dis, São Paulo, BrazilUniv Calif San Francisco, San Francisco Gen Hosp, Div HIV AIDS, San Francisco, CA USAUniv Calif San Francisco, Dept Expt Med, San Francisco, CA USASao Paula City Hlth Syst, São Paulo, BrazilUniversidade Federal de São Paulo, Div Infect Dis, São Paulo, BrazilBrazilian Program for STD and AIDS, Ministry of Health: 914/BRA/3014 UNESCO/KallasSão Paulo City Health Department: 2004-0.168.922-7/KallasFAPESP: 04/15856-9/KallasNIAID/NIH: AI066917/BarbourNIAID/NIH: AI064520/NixonJohn E. Fogarty International Center: D43 TW00003Web of Scienc