Defining the Critical Hurdles in Cancer Immunotherapy

ABSTRACT: Scientific discoveries that provide strong evidence of antitumor effects in preclinical models often encounter significant delays before being tested in patients with cancer. While some of these delays have a scientific basis, others do not. We need to do better. Innovative strategies need to move into early stage clinical trials as quickly as it is safe, and if successful, these therapies should efficiently obtain regulatory approval and widespread clinical application. In late 2009 and 2010 the Society for Immunotherapy of Cancer (SITC), convened an "Immunotherapy Summit" with representatives from immunotherapy organizations representing Europe, Japan, China and North America to discuss collaborations to improve development and delivery of cancer immunotherapy. One of the concepts raised by SITC and defined as critical by all parties was the need to identify hurdles that impede effective translation of cancer immunotherapy. With consensus on these hurdles, international working groups could be developed to make recommendations vetted by the participating organizations. These recommendations could then be considered by regulatory bodies, governmental and private funding agencies, pharmaceutical companies and academic institutions to facilitate changes necessary to accelerate clinical translation of novel immune-based cancer therapies. The critical hurdles identified by representatives of the collaborating organizations, now organized as the World Immunotherapy Council, are presented and discussed in this report. Some of the identified hurdles impede all investigators, others hinder investigators only in certain regions or institutions or are more relevant to specific types of immunotherapy or first-in-humans studies. Each of these hurdles can significantly delay clinical translation of promising advances in immunotherapy yet be overcome to improve outcomes of patients with cancer

2009 Influenza A(H1N1) seroconversion rates and risk factors among distinct adult cohorts in Singapore

10.1001/jama.2010.404JAMA - Journal of the American Medical Association303141383-139

Synthetic approaches to artificial photosynthesis: general discussion

Metals in Catalysis, Biomimetics & Inorganic Material

PROFIL WISATAWAN MUSEUM RADYA PUSTAKA SURAKARTA

Anggit Margaret, C9407031 2011. Profil Wisatawan Museum Radya Pustaka Surakarta. Program Studi Diploma III Usaha Perjalanan Wisata Fakultas Sastra Dan Seni Rupa Universitas Sebelas Maret Surakarta. Penelitian tugas akhir ini mengkaji tentang Profil Wisatawan di Museum Radya Pustaka Surakarta. Tujuan dari penelitian ini adalah untuk mengetahui dari daerah mana saja wisatawan yang berkunjung ke Museum Radya Pustaka, bagaimana ciri-ciri wisatawan yang berkunjung ke Museum Radya Pustaka serta harapan-harapan yang diinginkan wisatawan terhadap Museum Radya Pustaka. Penelitian dilakukan dengan metode kualitatif. Pengumpulan data dilakukan melalui wawancara dengan narasumber wisatawan yang berkujung di Museum Radya Pustaka Surakarta tempat penulis melakukan penelitian, serta studi pustaka dan studi dokumen guna menambah sumber data. Hasil penelitian menunjukkan bahwa (1) Sebagian besar wisatawan yang datang berasal dari Semarang sebesar 32%. (2) Mayoritas wisatawan yang berkunjung ke Museum Radya Pustaka berusia antara 17-25 tahun dan kebanyakan dari mereka adalah pelajar atau mahasiswa dengan prosentase 52%. (3) Sebagian besar wisatawan yang datang ke Museum Radya Pustaka adalah bertujuan untuk melakukan penelitian yaitu sebesar 34%. (4) Harapan wisatawan yang berkunjung terhadap kelangsungan Museum Radya Pustaka sebagian besar adalah agar ditingkatkan lagi pengelolaan dan keamanan museum, agar kejadian hilangnya benda-benda koleksi museum tidak terulang lagi dikemudian hari. Kesimpulan dari hasil penelitian ini bahwa wisatawan yang berkujung ke Museum Radya Pustaka Surakarta mayoritas berasal dari Semarang, mayoritas berusia 17-25 tahun dan kebanyakan dari mereka adalah berprofesi sebagai pelajar dan mahasiswa. Kebanyakan wisatawan yang datang bertujuan untuk melakukan penelitian, serta harapan wisatawan terhadap Museum Radya Pustaka adalah supaya lebih ditingkatkan lagi pengelolaan dan keamanan museum

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Biodegradation Of Pahs In Soil By Two Deuteromycete Fungi

The fungal strains used is this work, namely, 984 and 1040, were isolated fr om soil samples collected at the Jureia-Itatins Ecological Reserve, São Paulo-Brazil. Following microscopical examinations these strains were classified as Aspergillus sp. (984) and Verticillium sp. (1040). The degradation of PAHs in soil contaminated with 5 mg naphthalene/g soil; 1,0 mg anthracene/g soil or 0,5 mg pyrene and/or benzo[a]pyrene/g soil, was verified. These strains were grown in wheatbran:water for 3 days, inoculated in sterilized and non-sterilized soil, and cultivated for 2,4, 6, and 8 weeks. The PAHs were then extracted and degradation was determined by HPLC. The best degradation, in sterilized soil was obtained after 8 weeks for the two strains: naphthalene (64.50-65.43%), anthracene (77.35-85.83%) and pyrene (73.01-78.78%). When benzo[a]pyrene was used the best degradation shown by strain 984 was 89.62% in six weeks and 78.06% by strain 1040 in eight weeks. In non-sterilized soil the strains exhibited lower growth and degradation than in sterilized soil, with the exception for benzo[a]pyrene (82.3-82.6%). Our results indicate that these two fungal strains have potential for application in the bioremediation of soils contaminated with PAHs. © 2005 Springer Science + Business Media, Inc.91320Anderson, B.E., Henrysson, T., Accumulation and degradation of dead -end metabolites during treatment of soil contamined with polycyclic aromatic hydrocarbons with five strains of white-rot fungi (1996) Appl. Microbiol. Biotechnol., 46, pp. 647-652Andersson, B.E., Welinder, L., Olsson, P.A., Olsson, S., Henrysson, T., Growth of inoculated white -rot fungi and their interactions with the bacterial community in soil contaminated with poly cyclic aromatic hydrocarbons, as measured by phospholipid fatty acids (2000) Biores. Technol., 73, pp. 29-36Canet, R., Lopez-real, J., Beck, A.J., Overview of polycyclic aromatic hydrocarbons biodegradation by white-rot fungi (1999) Land Contam. Reclam., 7, pp. 191-197Canet, R., Birrnstingl, J.G., Malcom, D.G., Real-Lopez, J.M., Beck, A.J., Biodegradation of polycyclic aromatic hydrocarbons (pahs) by native microflora and combinations of white-rot fungi in a coal-tar contamined soil (2001) Biores. Technol., 76, pp. 113-117Clemente, A.R., Anazawa, T.A., Durrant, L.R., Biodegradation of polycyclic aromatic hydrocarbons by soil fungi (2001) Brazilian Journal of Microbiology, 32 (4), pp. 255-261. , BrasilClemente, A.R., Durrant, L.R., Degradation of PAHS by soil fungi with potential for bioremediation (2003) Proceedings in Situ and on -Site Bioremediation - The Seventh International Symposium, , Alleman, B. C. & Leeson, A. Eds., Columbus, Ohio, Battelle PressConte, P., Zena, A., Pilidis, G., Piccolo, A., Increased retention of polycyclic aromatic hydrocarbons in soils induced by soil treatment with humic substances (2001) Environ. Pollut., 112, pp. 27-31Ghoshal, S., Luthy, R.G., Bioavaialability of hydrophobic organic compounds from nonaqueus-phase liquids: The biodegrdation of naphthalene from coal tar (1996) Environ. Toxicol. Chem., 15, pp. 1894-1900Gustafson, K.E., Dikhut, R.M., Distribution of polycyclic aromatic hydrocarbons in southern chesapeake bay surface wate r: Evaluation of three methods for determining freely dissolved water concentrations (1995) Environ. Toxicol. Chem., 16, pp. 452-461Inder Wiesche, C., Martens, R., Zadrazil, F., Two-step degradation of pyrene by white-rot fungi and soil microorganisms (1996) Appl. Microbiol. Biotechnol., 46, pp. 653-659Kotterman, M.J.J., Vis, E.H., Field, J.A., Successive mineralization and detoxification of benzo[a]pyrene by the white -rot fungus bjerkandera sp. Strain BOS55 and indigenous microflora (1998) Appl. Environ. Microbiol., 64, pp. 2853-2858Lynch, J.M., Microorganisms in their natural environments - The terrestrial environment (1988) Micro-organisms in Action: Comcepts and Applications in Microbial Ecology, pp. 103-131. , Lynch, J. M. Hobbie, J. E. (Eds), Blackwell Scientific Publications, Paolo altoMartens, R., Zadrazil, F., Screening of white-rot fungi for their ability to mineralize polycyclic aromatic hydrocarbons in soil (1992) Preprints from the International Symposium on Soil Decontamination Using Biological Processes., pp. 505-510. , DECHEMA, Frankfurt am mainMurphy, E.M., Zachara, J.M., Smith, S.C., Influence of mineral-bound humic substances on the sorption of hydrophobic organic compounds (1990) Environ. Sci. Technol., 24, pp. 1507-1516Weissenfels, W.D., Klewer, H.J., Langhoff, J., Adsorption of polycyclic aromatic hydrocarbons (PAHS) by soil particles: Influence on biodegradability and biotoxicity (1992) Appl. Microbial. Biotechnol., 36, pp. 689-696Wilcock, R.J., Corban, G.A., Northcott, G.L., Wilkins, A.L., Langdon, A.G., Persistence of polycyclic aromatic compounds f different molecular size and water solubility in surficial sediment of an intertidal sandflat (1996) Environ. Toxicol. Chem., 15, pp. 670-67

Degradation Of Aromatic Pollutants By A Non-basidiomycete Ligninolytic Fungus

The bioremediation of PAH, compounds which are of great environmental and health concern, was studied using a non-basidiomycete ligninolytic fungus. A ligninolytic fungal strain (F 898) was grown in media containing either naphthalene, phenanthrene, anthracene, tannic acid, or phenol as the carbon source. Various levels of lignin peroxidase (LiP), manganese peroxidase (MnP) and laccase activities were detected following growth for three, six, and ten days. Indepependent of the carbon source, MnP activity levels were higher than LiP and laccase activities. Degradation (D) of the five PAH compounds, measured by reversed-phase HPLC on a C18 column, changed with each carbon source. Phenol and naphthalene were the least degraded compounds (D < 20%). Degradations for anthracene, phenanthrene, and tannic acid were respectively ~ 27%, 90%, and 100%.58