SIDO Buck converter with independent outputs

The portable electronics market is rapidly migrating towards more compact devices requiring multiple high-integrity high-efficiency voltage supplies for empowering the systems. This paper demonstrates a single inductor used in a buck converter with two output voltages from an input battery with voltage of value 3V. The main target is low cross regulation between the two outputs to supply independent load current levels while maintaining desired output voltage values well within a ripple that is set by adaptive hysteresis levels. A reverse current detector to avoid negative current flowing through the inductor prevents efficiency degradation at light load.Postprint (published version

Phase II multicohort study of atezolizumab monotherapy in multiple advanced solid cancers

PD-L1 checkpoint inhibitor; Atezolizumab; Solid tumorsInhibidor del punto de control PD-L1; Atezolizumab; Tumores sólidosInhibidor del punt de control PD-L1; Atezolizumab; Tumors sòlidsBackground The programmed death-ligand 1 inhibitor atezolizumab had shown clinical activity against several advanced malignancies. Patients and methods This phase II, open-label basket study (NCT02458638) was conducted in 16 main cohorts of patients aged ≥18 years with stage III or IV solid tumors. In stage I, 12 patients were enrolled into each cohort. Treatment was atezolizumab 1200 mg intravenously every 3 weeks until loss of clinical benefit or unacceptable toxicity. The primary efficacy endpoint was the non-progression rate (NPR) at 18 weeks in treated, assessable patients. NPR ≤20% was not of interest for development as monotherapy, and NPR ≥40% was defined as the threshold of benefit/success. If ≥3 patients had non-progressive disease in stage I (interim analysis), 13 additional patients could be enrolled into stage II (final analysis). Secondary efficacy and safety endpoints were also evaluated. Results Overall, 474 patients were enrolled and treated; 433 were included in the efficacy set. Due partly to slow recruitment because of competing trials and limited efficacy at interim analyses, enrollment was stopped early, including in cohorts that passed stage I boundaries of success. NPR was >20% in five cohorts: cervical cancer {n = 27; NPR 44.4% [95% confidence interval (CI) 25.5% to 64.7%]}; follicular/papillary thyroid cancer [n = 11; 54.5% (95% CI 23.4% to 83.3%)]; thymoma [n = 13; 76.9% (95% CI: 46.2% to 95.0%)]; gastroenteropancreatic (GEP) and lung neuroendocrine tumors [NETs; n = 24; 41.7% (95% CI 22.1% to 63.4%)], and low/intermediate grade carcinoid GEP and lung NETs [n = 12; 58.3% (95% CI 27.7% to 84.8%)]. Treatment-related adverse events occurred in 55.3% of patients overall, and at grade 3, 4, and 5 in 10.3%, 1.7%, and 0.4%, respectively. Conclusions Atezolizumab monotherapy was effective in the cervical cancer cohort. The interim benefit threshold was crossed in patients with follicular/papillary thyroid cancer, thymoma, and GEP and lung NETs, but recruitment was stopped before these signals could be confirmed in stage II. Safety was consistent with previous findings.This study was supported by F. Hoffmann-La Roche (no grant number) who provided financial support for the conduct of study and were involved in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the article for publication. They also funded assistance with manuscript writing by a professional medical writer

Ehrlichia chaffeensis Infection in the Reservoir Host (White-Tailed Deer) and in an Incidental Host (Dog) Is Impacted by Its Prior Growth in Macrophage and Tick Cell Environments

Citation: Nair, A. D. S., Cheng, C., Jaworski, D. C., Willard, L. H., Sanderson, M. W., & Ganta, R. R. (2014). Ehrlichia chaffeensis Infection in the Reservoir Host (White-Tailed Deer) and in an Incidental Host (Dog) Is Impacted by Its Prior Growth in Macrophage and Tick Cell Environments. PLOS ONE, 9(10), e109056. https://doi.org/10.1371/journal.pone.0109056Ehrlichia chaffeensis, transmitted from Amblyomma americanum ticks, causes human monocytic ehrlichiosis. It also infects white-tailed deer, dogs and several other vertebrates. Deer are its reservoir hosts, while humans and dogs are incidental hosts. E. chaffeensis protein expression is influenced by its growth in macrophages and tick cells. We report here infection progression in deer or dogs infected intravenously with macrophage- or tick cell-grown E. chaffeensis or by tick transmission in deer. Deer and dogs developed mild fever and persistent rickettsemia; the infection was detected more frequently in the blood of infected animals with macrophage inoculum compared to tick cell inoculum or tick transmission. Tick cell inoculum and tick transmission caused a drop in tick infection acquisition rates compared to infection rates in ticks fed on deer receiving macrophage inoculum. Independent of deer or dogs, IgG antibody response was higher in animals receiving macrophage inoculum against macrophage-derived Ehrlichia antigens, while it was significantly lower in the same animals against tick cell-derived Ehrlichia antigens. Deer infected with tick cell inoculum and tick transmission caused a higher antibody response to tick cell cultured bacterial antigens compared to the antibody response for macrophage cultured antigens for the same animals. The data demonstrate that the host cell-specific E. chaffeensis protein expression influences rickettsemia in a host and its acquisition by ticks. The data also reveal that tick cell-derived inoculum is similar to tick transmission with reduced rickettsemia, IgG response and tick acquisition of E. chaffeensis

Transmission Electron Microscopy Reveals Distinct Macrophage- and Tick Cell-Specific Morphological Stages of Ehrlichia chaffeensis

Background: Ehrlichia chaffeensis is an emerging tick-borne rickettsial pathogen responsible for human monocytic ehrlichiosis. Despite the induction of an active host immune response, the pathogen has evolved to persist in its vertebrate and tick hosts. Understanding how the organism progresses in tick and vertebrate host cells is critical in identifying effective strategies to block the pathogen transmission. Our recent molecular and proteomic studies revealed differences in numerous expressed proteins of the organism during its growth in different host environments. Methodology/Principal Findings: Transmission electron microscopy analysis was performed to assess morphological changes in the bacterium within macrophages and tick cells. The stages of pathogen progression observed included the attachment of the organism to the host cells, its engulfment and replication within a morulae by binary fission and release of the organisms from infected host cells by complete host cell lysis or by exocytosis. E. chaffeensis grown in tick cells was highly pleomorphic and appears to replicate by both binary fission and filamentous type cell divisions. The presence of Ehrlichia-like inclusions was also observed within the nucleus of both macrophages and tick cells. This observation was confirmed by confocal microscopy and immunoblot analysis. Conclusions/Significance: Morphological differences in the pathogen’s progression, replication, and processing within macrophages and tick cells provide further evidence that E. chaffeensis employs unique host-cell specific strategies in support of adaptation to vertebrate and tick cell environments

The complex TIE between macrophages and angiogenesis

Macrophages are primarily known as phagocytic immune cells, but they also play a role in diverse processes, such as morphogenesis, homeostasis and regeneration. In this review, we discuss the influence of macrophages on angiogenesis, the process of new blood vessel formation from the pre-existing vasculature. Macrophages play crucial roles at each step of the angiogenic cascade, starting from new blood vessel sprouting to the remodelling of the vascular plexus and vessel maturation. Macrophages form promising targets for both pro- and anti-angiogenic treatments. However, to target macrophages, we will first need to understand the mechanisms that control the functional plasticity of macrophages during each of the steps of the angiogenic cascade. Here, we review recent insights in this topic. Special attention will be given to the TIE2-expressing macrophage (TEM), which is a subtype of highly angiogenic macrophages that is able to influence angiogenesis via the angiopoietin-TIE pathway

Farmers’ Perception of Viral Diseases and Their Management in Pepper (Capsicum spp.) Production in Benin

Pepper (Capsicum spp.) is an important solanaceous cash crop in Benin; however, productivity is limited due to several key constraints, especially diseases caused by viruses. We sought to understand farmers’ perceptions of viral diseases, management strategies deployed, and to identify the virus population affecting pepper production in Benin. To assess farmers’ perceptions and management of viral diseases, a survey was carried out in four agroecological zones of Benin. A total of 144 pepper farmers were interviewed using the snowball method. A total of 52 pepper leaf samples with virus-like symptoms were collected and diagnosed by reverse-transcriptase polymerase chain reaction (RT-PCR) or PCR. Pepper production systems varied across agroecological zones (P ≤ 0.001) with a predominance of farms practicing monoculture (82%). The majority of farmers (89%) indicated that pests and diseases were the main constraints to increased production. Cucumber mosaic virus (92% of the total samples), Pepper vein yellow virus (52%), and Pepper veinal mottle virus (50%) were the major viruses detected in pepper fields in Benin. There were both single (29%) and mixed (71%) infections of the viruses, suggesting that mixed infections are common for pepper in Benin, confounding efforts to reduce virus infections. Nearly 100% of the farmers surveyed were not aware of these viral diseases. They also could not directly relate symptoms of virus infection to the presence of aphids, whiteflies, or thrips. Farmers relied primarily on synthetic insecticides (93%) to control virus vectors. Interestingly, some farmers applied commercial (12%) and homemade (17%) biopesticides, with neem-based preparations being the most widely used. A total of 15% of farmers used companion cropping with maize, mint or basil and 43% of farmers used crop rotation as a cultural management practice to control viral disease and vector pressure in pepper fields. The implications of this work include the importance of training farmers and extension agents on diagnosis of viruses and their vectors causing viral diseases. This study provides baseline information for the development of host-resistant cultivars and deployment of integrated pest management strategies for pepper in Benin to reduce farmer losses

Nanoscale temperature measurements using non-equilibrium Brownian dynamics of a levitated nanosphere

Einstein realised that the fluctuations of a Brownian particle can be used to ascertain properties of its environment. A large number of experiments have since exploited the Brownian motion of colloidal particles for studies of dissipative processes, providing insight into soft matter physics, and leading to applications from energy harvesting to medical imaging. Here we use optically levitated nanospheres that are heated to investigate the non-equilibrium properties of the gas surrounding them. Analysing the sphere's Brownian motion allows us to determine the temperature of the centre-of-mass motion of the sphere, its surface temperature and the heated gas temperature in two spatial dimensions. We observe asymmetric heating of the sphere and gas, with temperatures reaching the melting point of the material. This method offers new opportunities for accurate temperature measurements with spatial resolution on the nanoscale, and a new means for testing non-equilibrium thermodynamicsComment: 5 pages, 4 figures, supplementary material available upon reques