Contrasting Sea-Ice Algae Blooms in a Changing Arctic Documented by Autonomous Drifting Buoys

Novel observations of the seasonal evolution of an ice algal bloom on the Chukchi shelf were collected by two autonomous buoys deployed 180 km apart in first-year drifting sea ice. High attenuation of blue light in the bottom of the ice indicated considerable accumulation of ice algae biomass with derived Chlorophyll-a concentrations (Chl a) up to 184 mg m−2. Differences in the magnitude and persistence of ice algae biomass under each buoy appear to have been driven by differences in snow thickness, as ice thickness was similar between the sites. Minimal snow cover (0.02 m) around one buoy was associated with algae growth beginning in mid-May and lasting 70 days. The second buoy had notably more snow (0.4 m), causing ice algae production to lag behind the first site by approximately 4 weeks. The delay in growth diminished the peak of ice algae Chl a and duration compared to the first site. Light attenuation through the ice was intense enough at both buoys to have a potentially inhibiting impact on water column phytoplankton Chl a. Modeling ice algae growth with observed light intensities determined that nutrients were the limiting resource at the low snow site. In contrast, the algae at the high snow site were light-limited and never nutrient-limited. These data point toward changes in ice algae phenology with an earlier and longer window for growth; and nutrients rather than light determining the longevity and magnitude of production

Generation of orthotopic patient-derived xenografts from gastrointestinal stromal tumor.

BackgroundGastrointestinal stromal tumor (GIST) is the most common sarcoma and its treatment with imatinib has served as the paradigm for developing targeted anti-cancer therapies. Despite this success, imatinib-resistance has emerged as a major problem and therefore, the clinical efficacy of other drugs has been investigated. Unfortunately, most clinical trials have failed to identify efficacious drugs despite promising in vitro data and pathological responses in subcutaneous xenografts. We hypothesized that it was feasible to develop orthotopic patient-derived xenografts (PDXs) from resected GIST that could recapitulate the genetic heterogeneity and biology of the human disease.MethodsFresh tumor tissue from three patients with pathologically confirmed GISTs was obtained immediately following tumor resection. Tumor fragments (4.2-mm3) were surgically xenografted into the liver, gastric wall, renal capsule, and pancreas of immunodeficient mice. Tumor growth was serially assessed with ultrasonography (US) every 3-4 weeks. Tumors were also evaluated with positron emission tomography (PET). Animals were sacrificed when they became moribund or their tumors reached a threshold size of 2500-mm3. Tumors were subsequently passaged, as well as immunohistochemically and histologically analyzed.ResultsHerein, we describe the first model for generating orthotopic GIST PDXs. We have successfully xenografted three unique KIT-mutated tumors into a total of 25 mice with an overall success rate of 84% (21/25). We serially followed tumor growth with US to describe the natural history of PDX growth. Successful PDXs resulted in 12 primary xenografts in NOD-scid gamma or NOD-scid mice while subsequent successful passages resulted in 9 tumors. At a median of 7.9 weeks (range 2.9-33.1 weeks), tumor size averaged 473 ± 695-mm³ (median 199-mm3, range 12.6-2682.5-mm³) by US. Furthermore, tumor size on US within 14 days of death correlated with gross tumor size on necropsy. We also demonstrated that these tumors are FDG-avid on PET imaging, while immunohistochemically and histologically the PDXs resembled the primary tumors.ConclusionsWe report the first orthotopic model of human GIST using patient-derived tumor tissue. This novel, reproducible in vivo model of human GIST may enhance the study of GIST biology, biomarkers, personalized cancer treatments, and provide a preclinical platform to evaluate new therapeutic agents for GIST

Radiocarbon dating of the historic Livingstone Tree at Chiramba, Mozambique

Author Posting. © Studia Chemia, 2020. Studia Universitatis Babes-Bolyai Seria Chemia is an Open Access Journal (read, download, copy, distribute, print for research use, search, or link to the full texts of articles). The definitive version was published in Studia Universitatis Babes-Bolyai, Seria Chemia 65, no. 3 (2020): 149-156, doi:10.24193/subbchem.2020.3.11.The article reports the AMS (accelerator mass spectrometry) radiocarbon dating results of the Livingstone Tree, a large African baobab on the right bank of the Zambezi, near Chiramba, Mozambique. In 1858, David Livingstone, who discovered the baobab, carved his monogram on the walls of its inner cavity. In 1996, the historic baobab was uprooted when a cyclone struck the area. Several wood fragments were extracted from the remains of the toppled tree. Five samples which originate from these fragments were subsequently dated by radiocarbon. The oldest sample had a radiocarbon date of 1598 ± 17 BP, that corresponded in 1996 to a calibrated age of 1490 ± 35 calendar years. According to this value, the Livingstone Tree at Chiramba becomes one of the oldest known African baobabs, with an age of over 1500 years. The Livingstone Tree had a closed ring-shaped structure, that consisted of 4 fused stems around a false cavity and also 2 additional stems outside the ring.The research was funded by the Romanian Ministry of National Education CNCS-UEFISCDI under grants PN-II-ID-PCE-2013-76 and PN-III-P4-ID-PCE-2016-0776, Nr. 90/2017

Internet Queries and Methicillin-Resistant Staphylococcus aureus Surveillance

The Internet is a common source of medical information and has created novel surveillance opportunities. We assessed the potential for Internet-based surveillance of methicillin-resistant Staphylococcus aureus and examined the extent to which it reflects trends in hospitalizations and news coverage. Google queries were a useful predictor of hospitalizations for methicillin-resistant S. aureus infections

Veterans health administration hepatitis B testing and treatment with anti-CD20 antibody administration

AIM: To evaluate pretreatment hepatitis B virus (HBV) testing, vaccination, and antiviral treatment rates in Veterans Affairs patients receiving anti-CD20 Ab for quality improvement. METHODS: We performed a retrospective cohort study using a national repository of Veterans Health Administration (VHA) electronic health record data. We identified all patients receiving anti-CD20 Ab treatment (2002-2014). We ascertained patient demographics, laboratory results, HBV vaccination status (from vaccination records), pharmacy data, and vital status. The high risk period for HBV reactivation is during anti-CD20 Ab treatment and 12 mo follow up. Therefore, we analyzed those who were followed to death or for at least 12 mo after completing anti-CD20 Ab. Pretreatment serologic tests were used to categorize chronic HBV (hepatitis B surface antigen positive or HBsAg+), past HBV (HBsAg-, hepatitis B core antibody positive or HBcAb+), resolved HBV (HBsAg-, HBcAb+, hepatitis B surface antibody positive or HBsAb+), likely prior vaccination (isolated HBsAb+), HBV negative (HBsAg-, HBcAb-), or unknown. Acute hepatitis B was defined by the appearance of HBsAg+ in the high risk period in patients who were pretreatment HBV negative. We assessed HBV antiviral treatment and the incidence of hepatitis, liver failure, and death during the high risk period. Cumulative hepatitis, liver failure, and death after anti-CD20 Ab initiation were compared by HBV disease categories and differences compared using the χ2 test. Mean time to hepatitis peak alanine aminotransferase, liver failure, and death relative to anti-CD20 Ab administration and follow-up were also compared by HBV disease group. RESULTS: Among 19304 VHA patients who received anti-CD20 Ab, 10224 (53%) had pretreatment HBsAg testing during the study period, with 49% and 43% tested for HBsAg and HBcAb, respectively within 6 mo pretreatment in 2014. Of those tested, 2% (167/10224) had chronic HBV, 4% (326/7903) past HBV, 5% (427/8110) resolved HBV, 8% (628/8110) likely prior HBV vaccination, and 76% (6022/7903) were HBV negative. In those with chronic HBV infection, ≤ 37% received HBV antiviral treatment during the high risk period while 21% to 23% of those with past or resolved HBV, respectively, received HBV antiviral treatment. During and 12 mo after anti-CD20 Ab, the rate of hepatitis was significantly greater in those HBV positive vs negative (P = 0.001). The mortality rate was 35%-40% in chronic or past hepatitis B and 26%-31% in hepatitis B negative. In those pretreatment HBV negative, 16 (0.3%) developed acute hepatitis B of 4947 tested during anti-CD20Ab treatment and follow-up. CONCLUSION: While HBV testing of Veterans has increased prior to anti-CD20 Ab, few HBV+ patients received HBV antivirals, suggesting electronic health record algorithms may enhance health outcomes

Targeting LIF-mediated paracrine interaction for pancreatic cancer therapy and monitoring.

Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis largely owing to inefficient diagnosis and tenacious drug resistance. Activation of pancreatic stellate cells (PSCs) and consequent development of dense stroma are prominent features accounting for this aggressive biology1,2. The reciprocal interplay between PSCs and pancreatic cancer cells (PCCs) not only enhances tumour progression and metastasis but also sustains their own activation, facilitating a vicious cycle to exacerbate tumorigenesis and drug resistance3-7. Furthermore, PSC activation occurs very early during PDAC tumorigenesis8-10, and activated PSCs comprise a substantial fraction of the tumour mass, providing a rich source of readily detectable factors. Therefore, we hypothesized that the communication between PSCs and PCCs could be an exploitable target to develop effective strategies for PDAC therapy and diagnosis. Here, starting with a systematic proteomic investigation of secreted disease mediators and underlying molecular mechanisms, we reveal that leukaemia inhibitory factor (LIF) is a key paracrine factor from activated PSCs acting on cancer cells. Both pharmacologic LIF blockade and genetic Lifr deletion markedly slow tumour progression and augment the efficacy of chemotherapy to prolong survival of PDAC mouse models, mainly by modulating cancer cell differentiation and epithelial-mesenchymal transition status. Moreover, in both mouse models and human PDAC, aberrant production of LIF in the pancreas is restricted to pathological conditions and correlates with PDAC pathogenesis, and changes in the levels of circulating LIF correlate well with tumour response to therapy. Collectively, these findings reveal a function of LIF in PDAC tumorigenesis, and suggest its translational potential as an attractive therapeutic target and circulating marker. Our studies underscore how a better understanding of cell-cell communication within the tumour microenvironment can suggest novel strategies for cancer therapy

Muscarinic receptor-stimulated Ca2+ signaling and inositol lipid metabolism in avian salt gland cells

Activation of muscarinic cholinergic receptors was studied by measuring agonist-stimulated inositol lipid turnover and changes in [Ca2+]i in dissociated salt gland secretory cells. Carbachol stimulation of quin2-loaded cells results in a sustained 4-fold increase in [Ca2+]i, while incorporation of [32P]Pi into phosphatidylinositol (PI) and phosphatidate are similarly increased. [3H]Inositol phosphates, measured in the presence of Li+, increased 13-fold. The stimulated increment in [Ca2+]i required extracellular Ca2+, whereas [3H]inositol phosphate accumulation was independent of external Ca2+. Dose-response curves for carbachol-induced increments in [Ca2+]i, PI labeling, and labeled inositol phosphate release are similar, with EC50 values of 6, 4.5 and 8 [mu]M, respectively. Dissociation constants for atropine vs. the quin2 and phospholipid responses are 0.59 +/- 0.3 nM and 0.48 +/- 0.28 nM, respectively. These cells thus provide a model system for the study of non-exocytotic secretion as a consequence of stimulated inositol lipid turnover.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/25973/1/0000039.pd

A Holistic Systems Security Approach Featuring Thin Secure Elements for Resilient IoT Deployments

© 2020 by the authors. This is an open access article distributed under the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.IoT systems differ from traditional Internet systems in that they are different in scale, footprint, power requirements, cost and security concerns that are often overlooked. IoT systems inherently present different fail-safe capabilities than traditional computing environments while their threat landscapes constantly evolve. Further, IoT devices have limited collective security measures in place. Therefore, there is a need for different approaches in threat assessments to incorporate the interdependencies between different IoT devices. In this paper, we run through the design cycle to provide a security-focused approach to the design of IoT systems using a use case, namely, an intelligent solar-panel project called Daedalus. We utilise STRIDE/DREAD approaches to identify vulnerabilities using a thin secure element that is an embedded, tamper proof microprocessor chip that allows the storage and processing of sensitive data. It benefits from low power demand and small footprint as a crypto processor as well as is compatible with IoT 29 requirements. Subsequently, a key agreement based on an asymmetric cryptographic scheme, namely B-SPEKE was used to validate and authenticate the source. We find that end-to-end and independent stand-alone procedures used for validation and encryption of the source data originating from the solar panel are cost-effective in that the validation is carried out once and not several times in the chain as is often the case. The threat model proved useful not so much as a panacea for all threats but provided the framework for the consideration of known threats, and therefore appropriate mitigation plans to be deployed.Peer reviewe