Vascular Disrupting Agent Arsenic Trioxide Enhances Thermoradiotherapy of Solid Tumors

Our previous studies demonstrated arsenic trioxide- (ATO-) induced selective tumor vascular disruption and augmentation of thermal or radiotherapy effect against solid tumors. These results suggested that a trimodality approach of radiation, ATO, and local hyperthermia may have potent therapeutic efficacy against solid tumors. Here, we report the antitumor effect of hypofractionated radiation followed by ATO administration and local 42.5 °C hyperthermia and the effects of cisplatin and thermoradiotherapy. We found that the therapeutic efficacy of ATO-based thermoradiotherapy was equal or greater than that of cisplatin-based thermoradiotherapy, and marked evidence of in vivo apoptosis and tumor necrosis were observed in ATO-treated tumors. We conclude that ATO-based thermoradiotherapy is a powerful means to control tumor growth by using vascular disruption to augment the effects of thermal and radiation therapy

Public opinion on energy crops in the landscape: considerations for the expansion of renewable energy from biomass

Public attitudes were assessed towards two dedicated biomass crops – Miscanthus and Short Rotation Coppice (SRC), particularly regarding their visual impacts in the landscape. Results are based on responses to photographic and computer-generated images as the crops are still relatively scarce in the landscape. A questionnaire survey indicated little public concern about potential landscape aesthetics but more concern about attendant built infrastructure. Focus group meetings and interviews indicated support for biomass end uses that bring direct benefits to local communities. Questions arise as to how well the imagery used was able to portray the true nature of these tall, dense, perennial plants but based on the responses obtained and given the caveat that there was limited personal experience of the crops, it appears unlikely that wide-scale planting of biomass crops will give rise to substantial public concern in relation to their visual impact in the landscape

COVID-19 vaccination up-take in three districts of Nepal

Vaccine hesitancy during the COVID-19 pandemic continues to be an issue in terms of global efforts to decrease transmission rates. Despite high demand for the vaccines in Nepal, the country still contends with challenges related to vaccine accessibility, equitable vaccine distribution, and vaccine hesitancy. Study objectives were to identify: 1) up-take and intention for use of COVID-19 vaccines, 2) factors associated with vaccine up-take, and 3) trusted communication strategies about COVID-19 and the vaccines. A quantitative survey was implemented in August and September 2021 through an initiative at the Nepali Ministry of Health and Population Department of Health Services, Family Welfare Division. Data were collected from 865 respondents in three provinces (Bagmati, Lumbini, and Province 1). Ordinal multivariate logistic regression was utilized to determine relationships between vaccination status and associated factors. Overall, 62% (537) respondents were fully vaccinated and 18% (159) were partially vaccinated. Those respondents with higher education (p \u3c .001) and higher household income (p \u3c .001) were more likely vaccinated. There were also significant differences in vaccine up-take across the three provinces (p \u3c .001). Respondents who were vaccinated were significantly more likely to perceive vaccines as efficacious in terms of preventing COVID-19 (p = .004) and preventing serious outcomes (p = .010). Among both vaccinated and unvaccinated individuals, there was a high level of trust in information about COVID-19 vaccines provided through local health-care workers [e.g. nurses and physicians]. These results are consistent with other findings within the South Asia region. Targeted advocacy and outreach efforts are needed to support ongoing COVID-19 vaccination campaigns throughout Nepal

Evidence for Two Modes of Synergistic Induction of Apoptosis by Mapatumumab and Oxaliplatin in Combination with Hyperthermia in Human Colon Cancer Cells

Colorectal cancer is the third leading cause of cancer-related mortality in the world-- the main cause of death from colorectal cancer is hepatic metastases, which can be treated with isolated hepatic perfusion (IHP). Searching for the most clinically relevant approaches for treating colorectal metastatic disease by isolated hepatic perfusion (IHP), we developed the application of oxaliplatin concomitantly with hyperthermia and humanized death receptor 4 (DR4) antibody mapatumumab (Mapa), and investigated the molecular mechanisms of this multimodality treatment in human colon cancer cell lines CX-1 and HCT116 as well as human colon cancer stem cells Tu-12, Tu-21 and Tu-22. We showed here, in this study, that the synergistic effect of the multimodality treatment-induced apoptosis was caspase dependent and activated death signaling via both the extrinsic apoptotic pathway and the intrinsic pathway. Death signaling was activated by c-Jun N-terminal kinase (JNK) signaling which led to Bcl-xL phosphorylation at serine 62, decreasing the anti-apoptotic activity of Bcl-xL, which contributed to the intrinsic pathway. The downregulation of cellular FLICE inhibitory protein long isoform (c-FLIPL) in the extrinsic pathway was accomplished through ubiquitination at lysine residue (K) 195 and protein synthesis inhibition. Overexpression of c-FLIPL mutant (K195R) and Bcl-xL mutant (S62A) completely abrogated the synergistic effect. The successful outcome of this study supports the application of multimodality strategy to patients with colorectal hepatic metastases who fail to respond to standard chemoradiotherapy that predominantly targets the mitochondrial apoptotic pathway. © 2013 Song et al

Nanostructured carriers as innovative tools for cancer diagnosis and therapy

Cancer accounts for millions of deaths every year and, due to the increase and aging of the world population, the number of new diagnosed cases is continuously rising. Although many progresses in early diagnosis and innovative therapeutic protocols have been already set in clinical practice, still a lot of critical aspects need to be addressed in order to efficiently treat cancer and to reduce several drawbacks caused by conventional therapies. Nanomedicine has emerged as a very promising approach to support both early diagnosis and effective therapy of tumors, and a plethora of different inorganic and organic multifunctional nanomaterials have been ad hoc designed to meet the constant demand for new solutions in cancer treatment. Given their unique features and extreme versatility, nanocarriers represent an innovative and easily adaptable tool both for imaging and targeted therapy purposes, in order to improve the specific delivery of drugs administered to cancer patients. The current review reports an in-depth analysis of the most recent research studies aiming at developing both inorganic and organic materials for nanomedical applications in cancer diagnosis and therapy. A detailed overview of different approaches currently undergoing clinical trials or already approved in clinical practice is provided

Slip pulse and resonance of the Kathmandu basin during the 2015 Gorkha earthquake, Nepal.

This is the author accepted manuscript. The final version is available from AAAS via http://dx.doi.org/10.1126/science.aac6383Detailed geodetic imaging of earthquake ruptures enhances our understanding of earthquake physics and associated ground shaking. The 25 April 2015 moment magnitude 7.8 earthquake in Gorkha, Nepal was the first large continental megathrust rupture to have occurred beneath a high-rate (5-hertz) Global Positioning System (GPS) network. We used GPS and interferometric synthetic aperture radar data to model the earthquake rupture as a slip pulse ~20 kilometers in width, ~6 seconds in duration, and with a peak sliding velocity of 1.1 meters per second, which propagated toward the Kathmandu basin at ~3.3 kilometers per second over ~140 kilometers. The smooth slip onset, indicating a large (~5-meter) slip-weakening distance, caused moderate ground shaking at high frequencies (>1 hertz; peak ground acceleration, ~16% of Earth's gravity) and minimized damage to vernacular dwellings. Whole-basin resonance at a period of 4 to 5 seconds caused the collapse of tall structures, including cultural artifacts.The Nepal Geodetic Array was funded by internal funding to JPA from Caltech and DASE and by the Gordon and Betty Moore Foundation, through Grant GBMF 423.01 to the Caltech Tectonics Observatory and was maintained thanks to NSF Grant EAR 13-5136. Andrew Miner and the PAcific Northwest Geodetic Array (PANGA) at Central Washington University are thanked for technical assistance with the construction and operation of the Tribhuvan University-CWU network. Additional funding for the TU-CWU network came from United Nations Development Programme and Nepal Academy for Science and Technology. The high rate data were recovered thanks to a rapid intervention funded by NASA (US) and the Department of Foreign International Development (UK). We thank Trimble Navigation Ltd and the Vaidya family for supporting the rapid response as well. The accelerometer record at KATNP was provided by USGS. Research at UC Berkeley was funded by the Gordon and Betty Moore Foundation through grant GBMF 3024. A portion of this work was carried out at the Jet Propulsion Laboratory, California Institute of Technology, under a contract with the National Aeronautics and Space Administration. The GPS data were processed by ARIA (JPL) and the Scripps Orbit and Permanent Array Center. The effort at the Scripps Institution of Oceanography was funded by NASA grants NNX14AQ53G and NNX14AT33G. ALOS-2 data were provided under JAXA (Japan) PI Investigations 1148 and 1413. JPA thanks the Royal Society for support. We thank Susan Hough, Doug Given, Irving Flores and Jim Luetgert for contribution to the installation of this station

New and noteworthy lichen-forming and lichenicolous fungi 6

Eighteen new to science species, i.e.: 13 taxa from South Korea (Astroplaca loekoesiana S. Y. Kondr., E. Farkas, J.-J. Woo et J.-S. Hur, Buellia ulleungdoensis S. Y. Kondr., L. Lőkös et J.-S. Hur, Candelariella hakulinenii S. Y. Kondr., L. Lőkös et J.-S. Hur, Flavoplaca laszloana S. Y. Kondr. et J.-S. Hur, Lichenostigma epiporpidiae S. Y. Kondr., L. Lőkös et J.-S. Hur, Mikhtomia geumohdoensis S. Y. Kondr., Liu D. et J.-S. Hur, Orientophila dodongensis S. Y. Kondr., L. Lőkös et J.-S. Hur, Physcia orientostellaris S. Y. Kondr., L. Lőkös et J.-S. Hur, Placynthiella hurii S. Y. Kondr. et L. Lőkös, Protoparmeliopsis kopachevskae S. Y. Kondr., L. Lőkös et J.-S. Hur, Psoroglaena sunchonensis S. Y. Kondr., L. Lőkös et J.-S. Hur, Rufoplaca kaernefeltiana S. Y. Kondr., L. Lőkös et J.-S. Hur, Vezdaea poeltiana S. Y. Kondr., L. Lőkös, J. Halda et J.-S. Hur), two species from India (Rusavskia indica S. Y. Kondr. et D. K. Upreti, and R. upretii S. Y. Kondr., G. K. Mishra et S. Nayaka), and two species from Atlantic Europe, i.e.: Spain and Portugal (Xanthoria schummii S. Y. Kondr. and X. lapalmaensis F. Schumm et S. Y. Kondr.), as well as a lichenicolous fungus Leptosphaeria Oxneriae Cl. Roux et S. Y. Kondr. from Asia (Russia and India) are described, illustrated and compared with closely related taxa. Forty species of lichen forming and lichenicolous fungi (i.e.: Acarospora cf. rufescens, Agonimia allobata, A. aff. blumii, Anema decipiens, Anisomeridium aff. albisedum, Bacidia laurocerasi, Cercidospora aff. epipolytropa, C. aff. lobothallia, Dictyocatenulata alba, Fuscopannaria dissecta, Lecanora ussuriensis, Lecidella aff. carpatica, Lemmopsis arnoldiana, Leptosphaeria crozalsii, Lichenostigma cf. bolacinae, L. aff. rupicolae, Lichinella stipatula, L. cribellifera, L. iodopulchra, L. aff. myriospora, Melaspilea proximella, Micarea alabastrites, Opegrapha aff. thelotrematis, Orientophila leucerythrella, Pectenia plumbea, Placynthium tantaleum, Porpidia flavicunda, Psorula rufonigra, Pyrenocarpon aff. thelostomum, Pyrenodesmia duplicata, Pyrenopsis aff. haematina, Ramboldia haematites, Rhizoplaca subdiscrepans, Rimularia gibbosa, Rinodina oxydata, Staurothele frustulenta, Stigmidium cf. clauzadei, Strigula australiensis, Thelenella luridella, Vezdaea leprosa) are for the first time recorded for Korea. Additional locality records for South Korea (74 species) and China (3 species) are also given. Four new combinations, i.e.: Orientophila chejuensis (for Caloplaca chejuensis S. Y. Kondr. et Hur), Orientophila diffluens (for Lecanora diffluens Hue), Orientophila leucerythrella (for Lecanora leucerythrella Nyl.), and Pyrenodesmia duplicata (for Lecanora duplicata Vain.) are also proposed

Bioclimatic Architecture and Urban Morphology. Studies on Intermediate Urban Open Spaces

This paper deals with the interactions between biophysical and microclimatic factors on the one hand with, on the other, the urban morphology of intermediate urban open spaces, the relationship between environmental and bioclimatic thermal comfort, and the implementation of innovative materials and the use of greenery, aimed at the users’ well-being. In particular, the thermal comfort of the open spaces of the consolidated fabrics of the city of Rome is studied, by carrying out simulations of cooling strategies relating to two scenarios applied to Piazza Bainsizza. The first scenario involves the use of cool materials for roofs, cladding surfaces, and pavement, while the second scenario, in addition to the cool materials employed in the first scenario, also includes the use of greenery and permeable green surfaces. The research was performed using summer and winter microclimatic simulations of the CFD (ENVI-met v. 3.1) type, in order to determine the dierent influences of the materials with cold colors, trees, and vegetated surfaces on the thermal comfort of the urban morphology itself. Meanwhile, the comfort assessment was determined through the physiological equivalent temperature (PET) calculated with the RayMan program. The first scenario, with the use of cool materials, improves summer conditions and reduces the urban heat island eect but does not eliminate thermal discomfort due to the lack of shaded surfaces and vegetation. The second scenario, where material renovations is matched with vegetation improvements, has a slightly bad eect on winter conditions but drastically ameliorates the summer situation, both for direct users and, thanks to the strong reduction of the urban heat island eect, to urban inhabitants as a whole

Pleosporales

One hundred and five generic types of Pleosporales are described and illustrated. A brief introduction and detailed history with short notes on morphology, molecular phylogeny as well as a general conclusion of each genus are provided. For those genera where the type or a representative specimen is unavailable, a brief note is given. Altogether 174 genera of Pleosporales are treated. Phaeotrichaceae as well as Kriegeriella, Zeuctomorpha and Muroia are excluded from Pleosporales. Based on the multigene phylogenetic analysis, the suborder Massarineae is emended to accommodate five families, viz. Lentitheciaceae, Massarinaceae, Montagnulaceae, Morosphaeriaceae and Trematosphaeriaceae