Academic literature on the topic 'Human B-lineage ALL (B-ALL)'
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Journal articles on the topic "Human B-lineage ALL (B-ALL)"
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Uckun, FM, KJ Gajl-Peczalska, AJ Provisor, and NA Heerema. "Immunophenotype-karyotype associations in human acute lymphoblastic leukemia." Blood 73, no. 1 (January 1, 1989): 271–80. http://dx.doi.org/10.1182/blood.v73.1.271.271.
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Abstract The present study is a detailed analysis of the cytogenetic features of leukemic cells from 104 immunologically classified acute lymphoblastic leukemia (ALL) (78 B lineage and 26 T lineage) cases. Clonal chromosomal abnormalities were found in marrow blasts from 77 of 104 (74%) cases. Hyperdiploidy was much more frequent in B-lineage ALL cases, whereas normal diploidy was more common in T-lineage ALL cases. Fifty-nine of 104 cases (46 of 78 B-lineage ALL and 13 of 26 T-lineage ALL cases) had structural chromosomal abnormalities. Structural abnormalities involving 2p11, 7p13, 7p22, proximal q arm of 7 (7q11 or 7q22), 11q23–24, and translocations involving 12p11–13 appeared to be B- lineage specific. By comparison, structural abnormalities involving 7p15, 7q32, and 14q11 displayed T-lineage specificity. Structural abnormalities involving 9p22-p23 or 14q32, del (6)(q21-q23), del (12)(p11-p13), and the Philadelphia chromosome were found in B-lineage as well as T-lineage ALL cases. This study expands the current knowledge about immunophenotype-karyotype associations in ALL.
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Uckun, FM, KJ Gajl-Peczalska, AJ Provisor, and NA Heerema. "Immunophenotype-karyotype associations in human acute lymphoblastic leukemia." Blood 73, no. 1 (January 1, 1989): 271–80. http://dx.doi.org/10.1182/blood.v73.1.271.bloodjournal731271.
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The present study is a detailed analysis of the cytogenetic features of leukemic cells from 104 immunologically classified acute lymphoblastic leukemia (ALL) (78 B lineage and 26 T lineage) cases. Clonal chromosomal abnormalities were found in marrow blasts from 77 of 104 (74%) cases. Hyperdiploidy was much more frequent in B-lineage ALL cases, whereas normal diploidy was more common in T-lineage ALL cases. Fifty-nine of 104 cases (46 of 78 B-lineage ALL and 13 of 26 T-lineage ALL cases) had structural chromosomal abnormalities. Structural abnormalities involving 2p11, 7p13, 7p22, proximal q arm of 7 (7q11 or 7q22), 11q23–24, and translocations involving 12p11–13 appeared to be B- lineage specific. By comparison, structural abnormalities involving 7p15, 7q32, and 14q11 displayed T-lineage specificity. Structural abnormalities involving 9p22-p23 or 14q32, del (6)(q21-q23), del (12)(p11-p13), and the Philadelphia chromosome were found in B-lineage as well as T-lineage ALL cases. This study expands the current knowledge about immunophenotype-karyotype associations in ALL.
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Uckun, Fatih M., Lei Sun, Hong Ma, Sanjive Qazi, Ilker Dibirdik, and Zahide Ozer. "Targeting Human B-Precursor Acute Lymphoblastic Leukemia Cells with Recombinant Human CD19 Ligand." Blood 116, no. 21 (November 19, 2010): 599. http://dx.doi.org/10.1182/blood.v116.21.599.599.
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Abstract Abstract 599 CD19 is a 95-kDa B-lineage restricted receptor molecule that functions as a key regulator of transmembrane signals in both B-cells and B-cell precursors. Here we report the cloning and characterization of a novel high-mobility group (HMG)-box protein as the membrane-associated natural ligand of human CD19 receptor (CD19-L) on human immature as well as mature lymphoid cells. We cloned the gene encoding CD19-L from a human thymus cDNA library by yeast two-hybrid screening using the cDNA encoding human CD19 extracellular domain (AA 1 to 273) (CD19ECD) fused to the GAL4 DNA binding domain as the bait plasmid. The cDNA for the surface membrane-associated CD19-L protein is 2290-bp in length encoding a 487-aa protein with a predicted molecular mass of 54-kDa. The comparison of the amino acid sequence of CD19-L protein with reported sequences in Genebank Database revealed that CD19-L is a new member of the HMG-box protein family. CD19-L contains two leucine-rich hydrophobic nuclear export signal (NES) motifs associated with unconventional ER- and Golgi-independent transport of nuclear/cytoplasmic secretory proteins to the surface membrane. Expression of the CD19-L gene expression is limited to the lymphocyte compartment within the human lymphohematopoietic system and particularly abundant in T-lineage cells. CD19-L displays abundant expression on immature double-positive (DP) thymocytes as well as leukemic T-cell precursors from T-lineage ALL patients corresponding to immature double-negative (DN) pro-thymocyte and DP cortico-thymocyte stages of human T-cell ontogeny. CD19-L is also expressed on B-lineage lymphoid cells at all stages of human B-cell ontogeny, including fetal liver derived biphenotypic CD2+CD19+ pro-B/T cells, pro-B cells, pre-B cells and mature B-cells. Soluble recombinant human CD19-L protein produced in a baculovirus expression system exhibited exquisite specificity for the extracellular domain of CD19 and had profound effects on apoptosis-related signaling and gene expression in CD19+ human leukemia cells. Engagement of CD19 co-receptor on B-lineage ALL cells with soluble CD19-L protein perturbed CD19-associated signaling network and triggered tyrosine phosphorylation of CD19 in a time-dependent fashion with peak phosphorylation occurring within 1–5 min. CD19-phosphorylation was associated with rapid and transient activation of SYK tyrosine kinase. Treatment of B-lineage ALL cells with 100 ng/mL CD19-L for 24 h corrupted the regulation of gene expression and altered the expression levels of 13 genes directly involved in regulation of apoptosis. We next examined the ability of CD19-L to induce apoptosis in leukemic B-cell precursors from chemotherapy-resistant CD19-positive human B-lineage ALL cell lines NALM-6 (pre-B ALL), RS4;11 (MLL-AF4+ Pro-B ALL), and ALL-1 (BCR-ABL+ Pre-pre-B ALL). CD19-L (but not control proteins CD19ECD or CD19ICD) caused apoptosis in each of these 3 ALL cell lines. As CD19-L specifically targets CD19ECD, excess CD19ECD protein was able to compete with surface CD19 receptor for CD19-L binding and thereby prevent CD19-L induced apoptosis. Excess CD19 intracellular domain protein (CD19ICD) that was included as a negative control did not affect CD19-L induced apoptosis. CD19-L was also capable of causing apoptosis in chemotherapy-resistant primary leukemic cells from relapsed CD19+ B-lineage ALL patients. This collection of experimental data provides compelling evidence that CD19-L is a potent biotherapeutic new agent candidate against CD19+ lymphoid malignancies. The identification of human CD19-L may lead to therapeutic innovation for B-lineage ALL as well as other B-lineage lymphoid malignancies by providing an effective alternative to CD19-directed monoclonal antibody-based biotherapeutic agents that have encountered several limitations in clinical settings. Disclosures: No relevant conflicts of interest to declare.
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Dovat, Sinisa, Chunhua Song, and Kimberly Payne. "Ikaros directly upregulates transcription of B lineage-specific genes in human B cell leukemia (P4412)." Journal of Immunology 190, no. 1_Supplement (May 1, 2013): 52.26. http://dx.doi.org/10.4049/jimmunol.190.supp.52.26.
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Abstract Ikaros encodes a DNA-binding protein that functions as a master regulator of hematopoiesis and a tumor suppressor in pre-B acute lymphoblastic leukemia (B-ALL). Loss of Ikaros function is associated with impaired hematopoiesis and high-risk B-ALL in humans. The mechanism of Ikaros tumor suppressor activity is unknown. Using quantitative chromatin immunoprecipitation (qChIP) we demonstrate that Ikaros binds to the promoters of genes required for B cell differentiation in primary leukemia cells. Luciferase reporter assays demonstrated that Ikaros activates transcription of these B lineage-specific genes. Increased expression of Ikaros via retroviral transduction in B-ALL cells resulted in increased transcription of these critical B cell differentiation genes, as well as increased binding of Ikaros to their promoters. The inhibition of Casein Kinase II (CK2) resulted in dephosphorylation of Ikaros and enhanced Ikaros-mediated transcriptional activation of the B lineage-specific genes in B-ALL. Treatment of the pre-B ALL cell line, Nalm6, with a CK2 inhibitor, resulted in increased Ikaros binding to the promoters of B lineage genes, increased transcription of B cell differentiation genes, and cell cycle arrest. Results suggest that Ikaros functions as a positive regulator of B cell differentiation by directly upregulating the transcription of B lineage-specific genes in B-ALL. The presented data suggest that CK2 has a critical role in B cell differentiation and in leukemogenesis.
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Sung Min, Woo, Chang W. Song, and Fatih M. Uckung. "Thermal sensitivity and thermal tolerance of human b-lineage acute lymphoblastic leukemia (all) cells." International Journal of Radiation Oncology*Biology*Physics 18, no. 1 (January 1990): 147–53. http://dx.doi.org/10.1016/0360-3016(90)90278-r.
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Koss, Brian, Jeffrey Morrison, Rhonda M. Perciavalle, Harpreet Singh, Jerold E. Rehg, Richard T. Williams, and Joseph T. Opferman. "Requirement for antiapoptotic MCL-1 in the survival of BCR-ABL B-lineage acute lymphoblastic leukemia." Blood 122, no. 9 (August 29, 2013): 1587–98. http://dx.doi.org/10.1182/blood-2012-06-440230.
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Key Points Using a mouse genetic mouse model of Ph+ B-lineage ALL, endogenous antiapoptotic MCL-1 is required for leukemia survival. In BCR-ABL+ B-lineage ALL human and mouse cells, combining TKIs with small-molecule inhibitors of BCL-2 can potentiate sensitivity to cell death.
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Herfst, Sander, Vicente Mas, Lorena S. Ver, Rutger J. Wierda, Albert D. M. E. Osterhaus, Ron A. M. Fouchier, and José A. Melero. "Low-pH-Induced Membrane Fusion Mediated by Human Metapneumovirus F Protein Is a Rare, Strain-Dependent Phenomenon." Journal of Virology 82, no. 17 (July 2, 2008): 8891–95. http://dx.doi.org/10.1128/jvi.00472-08.
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ABSTRACT Membrane fusion promoted by human metapneumovirus (HMPV) fusion (F) protein was suggested to require low pH (R. M. Schowalter, S. E. Smith, and R. E. Dutch, J. Virol. 80:10931-10941, 2006). Using prototype F proteins representing the four HMPV genetic lineages, we detected low-pH-dependent fusion only with some lineage A proteins and not with lineage B proteins. A glycine at position 294 was found responsible for the low-pH requirement in lineage A proteins. Only 6% of all HMPV lineage A F sequences have 294G, and none of the lineage B sequences have 294G. Thus, acidic pH is not a general trigger of HMPV F proteins for activity.
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Uckun, FM, K. Gajl-Peczalska, DE Myers, W. Jaszcz, S. Haissig, and JA Ledbetter. "Temporal association of CD40 antigen expression with discrete stages of human B-cell ontogeny and the efficacy of anti-CD40 immunotoxins against clonogenic B-lineage acute lymphoblastic leukemia as well as B- lineage non-Hodgkin's lymphoma cells." Blood 76, no. 12 (December 15, 1990): 2449–56. http://dx.doi.org/10.1182/blood.v76.12.2449.bloodjournal76122449.
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Detailed immunophenotypic analyses of immunologically classified leukemias and lymphomas showed that CD40 displays an exquisite B- lineage specificity within the human lymphopoietic system. Notably, 82% of B-lineage chronic lymphocytic leukemias (CLLs), 82% of B-lineage hairy cell leukemias (HCLs), 86% of B-lineage non-Hodgkin's lymphomas (NHLs), and 29% of B-lineage acute lymphoblastic leukemias (ALLs) were CD40+. Quantitative analyses of the correlated expression of CD40 and other B-lineage differentiation antigens on fetal lymphoid precursor cells by multiparameter two-color/three-color flow cytometry, combined with analyses of sequential antigen expression on fluorescence- activated cell fluorescence activated cell sorter (FACS) isolated immunologically distinct fetal B-cell precursor subpopulations during in vitro proliferation and differentiation, provided evidence that the acquisition of CD40 antigen in human B-cell ontogeny occurs subsequent to the expression of CD10 and CD19 antigens but before the surface expression of CD20, CD21, CD22, CD24, and surface immunoglobulin M (sIgM). Some leukemic pro-B cells from ALL patients as well as normal pro-B cell clones from fetal livers displaying germline Ig heavy chain genes were CD40+, indicating that the acquisition of CD40 antigen likely precedes the rearrangement of Ig heavy chain genes. CD40+ FACS- sorted malignant cells from B-lineage ALL as well as B-lineage NHL patients were capable of in vitro clonogenic growth, indicating the CD40 antigen is expressed on clonogenic leukemia and lymphoma cells. This hypothesis was confirmed by the ability of an anti-CD40 immunotoxin that we used as an antigen-specific cytotoxic probe to effectively kill clonogenic B-lineage ALL and NHL cells.
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Uckun, Fatih, Ilker Dibirdik, Sanjive Qazi, and Seang Yiv. "Therapeutic nanoparticle constructs of a JAK3 tyrosine kinase inhibitor against human B-lineage ALL cells." Arzneimittelforschung 60, no. 04 (December 2, 2011): 210–17. http://dx.doi.org/10.1055/s-0031-1296275.
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Uckun, FM, K. Gajl-Peczalska, DE Myers, W. Jaszcz, S. Haissig, and JA Ledbetter. "Temporal association of CD40 antigen expression with discrete stages of human B-cell ontogeny and the efficacy of anti-CD40 immunotoxins against clonogenic B-lineage acute lymphoblastic leukemia as well as B- lineage non-Hodgkin's lymphoma cells." Blood 76, no. 12 (December 15, 1990): 2449–56. http://dx.doi.org/10.1182/blood.v76.12.2449.2449.
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Abstract Detailed immunophenotypic analyses of immunologically classified leukemias and lymphomas showed that CD40 displays an exquisite B- lineage specificity within the human lymphopoietic system. Notably, 82% of B-lineage chronic lymphocytic leukemias (CLLs), 82% of B-lineage hairy cell leukemias (HCLs), 86% of B-lineage non-Hodgkin's lymphomas (NHLs), and 29% of B-lineage acute lymphoblastic leukemias (ALLs) were CD40+. Quantitative analyses of the correlated expression of CD40 and other B-lineage differentiation antigens on fetal lymphoid precursor cells by multiparameter two-color/three-color flow cytometry, combined with analyses of sequential antigen expression on fluorescence- activated cell fluorescence activated cell sorter (FACS) isolated immunologically distinct fetal B-cell precursor subpopulations during in vitro proliferation and differentiation, provided evidence that the acquisition of CD40 antigen in human B-cell ontogeny occurs subsequent to the expression of CD10 and CD19 antigens but before the surface expression of CD20, CD21, CD22, CD24, and surface immunoglobulin M (sIgM). Some leukemic pro-B cells from ALL patients as well as normal pro-B cell clones from fetal livers displaying germline Ig heavy chain genes were CD40+, indicating that the acquisition of CD40 antigen likely precedes the rearrangement of Ig heavy chain genes. CD40+ FACS- sorted malignant cells from B-lineage ALL as well as B-lineage NHL patients were capable of in vitro clonogenic growth, indicating the CD40 antigen is expressed on clonogenic leukemia and lymphoma cells. This hypothesis was confirmed by the ability of an anti-CD40 immunotoxin that we used as an antigen-specific cytotoxic probe to effectively kill clonogenic B-lineage ALL and NHL cells.
Dissertations / Theses on the topic "Human B-lineage ALL (B-ALL)"
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Caeser, Rebecca. "Elucidating oncogenic mechanisms in human B cell malignancies." Thesis, University of Cambridge, 2018. https://www.repository.cam.ac.uk/handle/1810/285011.
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This study consists of two pieces of work investigating haematological malignancies; Acute Lymphoblastic Leukaemia (ALL) and Diffuse Large B Cell Lymphoma (DLBCL). Firstly, Pre-B ALL represents the most common paediatric malignancy and despite increasingly improved outcomes for patients, ~ 20% of all patients diagnosed with ALL relapse. Activating mutations in the RAS pathway are common (~50%) and result in hyperactivation of the MAPK pathway. I identified Erk negative feedback control via DUSP6 to be crucial for NRASG12D-mediated pre-B cell transformation and investigated its potential as a therapeutic target. I showed that a small molecule inhibitor of DUSP6 (BCI) selectively induced cell death in patient-derived pre-B ALL cells; with a higher sensitivity observed in relapse pre-B ALL. I also discovered that a high level of Erk activity is required for proliferation of normal pre-B cells, but dispensable in leukemic pre-B ALL cells. In addition, I found that human B cell malignancies can be grouped into three categories that fundamentally differ in their ability to control Erk signalling strength. Secondly, DLBCL is the most common haematological malignancy and although potentially curable with chemotherapy, 40% of patients still succumb from their disease. Recent exome sequencing studies have identified hundreds of genetic alterations but, for most, their contribution to disease, or their importance as therapeutic targets, remains uncertain. I optimised a novel approach to screen the functional importance of these mutations. This was achieved by reconstituting non-malignant, primary, human germinal centre B cells (GC B cells) with combinations of wildtype and mutant genes to recapitulate the genetic events of DLBCL. When injected into immunodeficient mice, these oncogene-transduced GC B cells gave rise to tumours that closely resemble human DLBCL, reinforcing the biological relevance of this system. To screen potential tumour suppressor mutations in this system in a high throughput fashion, I developed a lymphoma-focused CRISPR library of 692 genes recurrently altered in B cell lymphomas. These experiments identified GNA13 as an unexpectedly potent tumour suppressor in human GC B cells and provided new understanding to its mechanism of action. These findings provide novel understanding of the complexity of oncogenic mechanisms in human B cell malignancies.
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Whelan, Jarrett Bertrand Fred. "Enforced Expression of Hoxa9 in B-Lineage All Promotes Survival and Proliferation of Leukemic Cells." [Greenville, N.C.] : East Carolina University, 2009. http://hdl.handle.net/10342/1903.
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郑健 and Jian Zheng. "Generation of human allo-antigen specific CD4+ and CD8+ regulatory T cells with CD40-activated B cells." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2011. http://hub.hku.hk/bib/B46922969.
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Della, Marina Filippo. "Dissection of the function and pre-clinical targeting of IGF1R in Acute Lymphoblastic Leukemia induced by the BCR-ABL fusion oncoprotein." Sorbonne Paris Cité, 2015. http://www.theses.fr/2015USPCC309.
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Contrairement aux réponses cliniques favorables chez les patients porteurs de Leucémie Myéloïdes Chronique traités avec des inhibiteurs ciblant l'activité tyrosine kinase de l'oncoprotéine de fusion BCR-ABL, les Leucémie Aigues Lymphoblastiques (LAL-B) BCR-ABL-positives restent de mauvais pronostic et requièrent de nouvelles stratégies thérapeutiques. Cette situation résulte de la présence d'autres altérations génétiques récurrentes, telle que la délétion mono- ou bi-allélique du gène codant le facteur de transcription Ikaros, observée dans plus de 83% des patients. Notre laboratoire a créé un modèle murin permettant l'analyse des conséquences de la perte de fonction d'Ikaros dans les LAL-B BCR-ABL+, et identifié une signature transcriptomique liée à l'absence d'un allèle sauvage d'Ikaros dans ces cellules. Cette signature transcriptomique inclut la surexpression du récepteur tyrosine kinase IGF1R. Mon travail de thèse montre : (i) que l'inhibition pharmacologique de IGF1R sensibilise les LAL-B BCR-ABL+ déficientes pour Ikaros aux effets antiprolifératifs et pro-apoptotiques de Nilotinib, (ii) que la délétion du gène IGF1R inhibe l'expansion de ces cellules in vivo, (iii) que le traitement des souris leucémiques avec NVP-AEW541 (un inhibiteur de IGF1R) en combinaison avec Nilotinib augmente significativement la survie des souris traitées par rapport aux souris contrôles, (iv) que l'augmentation de la survie des souris traitées est accompagnée par une augmentation de l'apoptose et une diminution de la prolifération des cellules leucémiques, et (v) que la voie AKT/mTORC1/S6K est une cible moléculaire de cette combinaison d'inhibiteursIn recent years several inhibitors have been developed targeting the tyrosine kinase activity of the BCR-ABL fusion oncoprotein in Chronic Myeloid Leukemia (CML). Unlike the favorable clinical response observed in CML cases, BCR¬ABL` B-cell Acute Lymphoblastic Leukemias (B-ALLs) remain of poor prognosis. The likely reason for this aggressive behavior is the presence in these leukemias of additional genetic alterations. The most frequent of these is the mono-or bi-allelic deletion of the gene encoding the Ikaros transcription factor (IKZF1), observed in over 83% of patients. Our laboratory has studied the functional consequences of IKZF1 haploinsufficiency in a BCR-ABL-induced B-ALL mouse model and identified an Ikaros-dependent transcriptomic signature in these leukemic cells. This signature includes the overexpression of IGF1R, a tyrosine kinase receptor for IGF1. Based on these premises my PhD thesis work shows (i) that pharmacological inhibition of IGF1R sensitizes Ikaros-deficient BCR-ABL+ B-ALL to the antiproliferative and pro-apoptotic effects of Nilotinib, (ii) that IGF1R gene deletion impairs in vivo expansion of these leukemias in vivo, (iii) that treatment of leukemic mice with NVP-AEW541 (an IGF1R inhibitor) in combination with Nilotinib significantly increases survival of treated mice as compared to control mice, (iv) that the increased survival of treated mice is accompanied by an increase in apoptosis and a decrease in the proliferation of leukemic cells and (v) that inhibition of the AKT/mTORC1/S6K signalling pathway is a point of convergence of these inhibitor combination
Books on the topic "Human B-lineage ALL (B-ALL)"
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Berkson, Burt. All about B vitamins. Garden City Park, N.Y: Avery, 1998.
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Berkson, Burt. All about B vitamins. Garden City Park, N.Y: Avery, 1998.
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Schöck, Cornelia. Jahm b. Ṣafwān (d. 128/745–6) and the ‘Jahmiyya’ and Ḍirār b. ʿAmr (d. 200/815). Edited by Sabine Schmidtke. Oxford University Press, 2014. http://dx.doi.org/10.1093/oxfordhb/9780199696703.013.28.
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The chapter is a first step on the way to classify the earliest Muslim theologians according to their position and role in the history of natural theology and philosophy. It argues that Jahm b. Ṣafwān and Ḍirār b. ʿAmr represent an empiristic theory according to which the sensible reality outside the mind corresponds one-to-one to the perception inside the human mind. God’s creation is by composition of bundles of properties; man’s knowledge is by decomposition of the property bundles into their parts by means of perception. The perceptions of substantial and qualitative change supply the empirical data by which the intuition of God as the cause of all generation, corruption, and change in corporeal things happens. They refuse a principle of form and essence in things as well as natural causes and powers of generation and alteration in the created cosmos.
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Brogger, Jan. Pre-Bureaucratic Europeans: A Study of a Portuguese Fishing Community (Institute for Comparative Research in Human Culture, Oslo. Serie B : Skrifter). A Scandinavian University Press Publication, 1990.
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Pitkin, John Budd, and Daniel Baker. Discourse, Embracing Several Important Objections to the Doctrine That Jesus Christ As Mediator Posseses Two Natures: The Divine and Human, in Mysterious, yet All Harmonious Union; in Reply to a Recently Published Sermon, Delivered by the Rev. Daniel B. Creative Media Partners, LLC, 2018.
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Cox, F. E. G. Babesiosis and malaria. Oxford University Press, 2011. http://dx.doi.org/10.1093/med/9780198570028.003.0055.
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Babesiosis and malaria are rare zoonoses that, with new developments in diagnosis and the application of molecular techniques, are becoming increasingly frequently recognised. Babesia species infect millions of cattle and unknown numbers of sheep, dogs, horses, and wildlife throughout the world but human infections are very uncommon. There are two distinct forms of human babesiosis. In Europe the causative agent is Babesia divergens, a natural parasite of cattle transmitted by the tick Ixodes ricinis. B. divergens infections in humans are extremely rare and nearly all have been recorded from asplenic or otherwise immunocompromised patients. In the USA, human babesiosis is more common than in Europe, although still very rare, and is not restricted to immunocompromised individuals. The causative agents are Babesia microti and B. duncani, common parasites of rodents, transmitted by the tick Ixodes scapularis. In addition there have been sporadic reports of human babesiosis from other parts of the world but in most cases the species of Babesia involved has not been characterised. Malaria parasites and Babesia both inhabit red blood cells during part of their life cycles and these stages cause the diseases, malaria and babesiosis, which are similar in many respects. The facts that humans can occasionally acquire malaria and babesiosis from animals, that both parasites appear similar when seen in blood films and that both cause similar symptoms can cause problems in diagnosis and these rare infections are, therefore, of interest to clinicians and epidemiologists.
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Treiger, Alexander. Origins of. Edited by Sabine Schmidtke. Oxford University Press, 2014. http://dx.doi.org/10.1093/oxfordhb/9780199696703.013.001.
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This article investigates the origins ofKalāmin the debate culture of Late Antiquity. Following Michael Cook and Jack Tannous, it argues thatkalām-style argumentation has its origin in Christological debates and was then absorbed into Muslim practice through the mediation of the Arab Christian milieu in Syria and Iraq. The second part of the article considers the origins of theQadardebate (human free will versus divine predestination). Finally, the third part discusses three Muslim texts onQadar, falsely attributed to Ḥasan b. Muḥammad b. al-Ḥanafiyya, ‘Umar b. ‘Abd al-’Azīz, and al-Ḥasan al-Baṣrī. It offers a critical appraisal of Josef van Ess’s reconstruction of the ‘beginnings’ ofKalām.
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Griffith, Sidney H. Yaḥyā b. ʿAdī’s (d. 974). Edited by Khaled El-Rouayheb and Sabine Schmidtke. Oxford University Press, 2016. http://dx.doi.org/10.1093/oxfordhb/9780199917389.013.6.
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The tenth-century Baghdadi Christian logician and philosopher Yaḥyā ibn ‘Adī (893–974) composed his Tahdhib al-akhlaq, The Reformation of Morals, as a popular treatise on virtue ethics in the spirit of his teacher, the Muslim philosopher Abu Nasr al-Farabi (870–950). Over the centuries it has gained a wide readership among both Muslims and Christians living in the Islamic world. The author outlines the profile of the virtuous “Perfect Man” and of “humane” behavior (al-insāniyya), as well as highlighting the complimentary roles of rulers and scholars in a virtuous society.
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Westerhoff, Jan. The Non-Existence of the Real World. Oxford University Press, 2020. http://dx.doi.org/10.1093/oso/9780198847915.001.0001.
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The book is concerned with the existence of the real world, that is, with the existence of a world of objects that exist independent of human interests, concerns, and cognitive activities. The main thesis defended is that we have good reason to deny the existence of such a world. The discussion is concerned with four main facets of assuming a real world: (a) the existence of an external world of physical objects in space and time; (b) the existence of an internal world, comprising various mental states congregated around a self; (c) the existence of an ontological foundation that grounds the existence of all the entities in the world; and (d) the existence of an ultimately true theory that provides a final account of all there is. I argue specifically that: (a) we should reject the postulation of an external world behind our representations; (b) the internal world is not as epistemically transparent as is usually assumed, and there is no substantial self acting as central unifier of our mental lives; (c) there are good reasons for adopting an anti-foundational account of ontological dependence; and (d) ontology, and philosophy more generally, must not be conceived of as providing an ultimately true theory of the world.
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Smedley, Julia, Finlay Dick, and Steven Sadhra. Non-chemical emergencies. Oxford University Press, 2013. http://dx.doi.org/10.1093/med/9780199651627.003.0040.
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Management of anaphylaxis 814Management of needlestick and contamination incidents 1 816Management of needlestick and contamination incidents 2: hepatitis B virus post-exposure prophylaxis 820Management of needlestick and contamination incidents 3: human immunodeficiency virus post-exposure prophylaxis 822Psychiatric emergencies 824In OH practice, anaphylaxis can occur in association with the administration of immunizations. All OH departments that administer vaccines must have adequate facilities for resuscitation. Resuscitation equipment should be latex free, particularly in the health care industry where the incidence of type 1 hypersensitivity to latex among employees is significant. OH staffs who administer vaccines should be retrained in resuscitation protocols annually....
Book chapters on the topic "Human B-lineage ALL (B-ALL)"
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Baersch, G., T. Möllers, A. Hötte, B. Dockhorn-Dworniczak, Ch Rübe, J. Ritter, H. Jürgens, and J. Vormoor. "Evaluation Of NOD-SCID-Mice for a Human B-Cell Precursor ALL Xenograft Model." In Haematology and Blood Transfusion / Hämatologie und Bluttransfusion, 73–77. Berlin, Heidelberg: Springer Berlin Heidelberg, 1998. http://dx.doi.org/10.1007/978-3-642-71960-8_10.
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Tudor, Maria Cristiana, Ursa Bernardic, Nina M. Sooter, and Giuseppe Ugazio. "Behavioral Perspectives on B Corps." In The International Handbook of Social Enterprise Law, 233–79. Cham: Springer International Publishing, 2022. http://dx.doi.org/10.1007/978-3-031-14216-1_12.
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AbstractThe values driving entrepreneurs are evolving from shareholder wealth maximization towards a more holistic approach wherein business impacts on all stakeholders are considered. This change has been driven in part by a societal cultural shift focused on promoting a sustainable future. To meet this cultural change demanding a balance of profit and ethics, novel entities (e.g., B Corps) have emerged in the private sector. In this chapter, we engage with behavioral perspectives to explore B Corps’ achievements, opportunities, and challenges. We first outline the transition from shareholder to stakeholder considerations, as we believe it constitutes the philosophical ethos of social enterprises. We then focus in turn on four of the five areas used by B Lab’s Impact Assessment—governance, workers, customers and consumers, and community—as they are most appropriate for an exploratory analysis of their interaction with human behavior. Specifically, in governance, we approach the topic of corporate ethics and transparency, as well as how the values of social entrepreneurs shape a firm’s culture. We then outline the relationship between purposeful work and employee performance and examine how B Corps have applied effective practices on social inclusion and employee well-being, in the workers’ section. Concerning customers and consumers, we explore a range of perspectives, including consumer motivations to purchase from B Corps, caveats of ethical consumerism, and how B Corps can capitalize on decision-making research to inspire consumer change. Additionally, we present our research on public awareness and perceptions of B Corp trustworthiness and greenwashing. Finally, the last section—community—highlights B Corps’ civic engagement and communication with their communities through social media, corporate volunteering, and charity work, among others.
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Fernandes, Ashley K. "The Rights and Responsibilities of the Physician to Uphold Bioethical Values in Society." In The International Library of Bioethics, 247–59. Cham: Springer International Publishing, 2022. http://dx.doi.org/10.1007/978-3-031-01987-6_14.
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AbstractIn this chapter, I will reflect on medical ethics after the Holocaust by focusing on the rights and responsibilities of the physician to uphold bioethical values in society—which must transcend cultural, professional, and institutional mores. Physicians can do so only if: (a) They are called back to the value of the human person and the physician’s primary duty to uphold his or her good. (b) They acknowledge the hierarchical structure of medical education and resist reflexively the temptation to succumb to its moral dictates. (c) They promote a vigorous right of conscientious objection (CO), so that, if the time comes, they can defend their call to heal even against external pressures from the state, scientific establishment, and/or culture. (d) Finally, they remember those who suffered in the Holocaust both to honor them, and to remind physicians of what the power of medicine has done to degrade dignity, and what it has the potential to do to advance the dignity of all human persons.
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Goodpaster, Kenneth E. "The Common Good and the Anthropological Insight." In Times of Insight: Conscience, Corporations, and the Common Good, 39–48. Cham: Springer International Publishing, 2022. http://dx.doi.org/10.1007/978-3-031-09712-6_4.
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AbstractIn this chapter, I take up the insufficiency of the stockholder-stakeholder debate characteristic of business ethics in its earlier years. I argue that this debate rarely goes deeply enough: to a more comprehensive picture of the human person, a more robust account of the good. This is not optional—if such a more robust account of the good is not made explicit in a normative view of ethics, it inevitably enters beneath the surface, without being made explicit. The sources for more comprehensive accounts of the human person lie in moral traditions that we have inherited, faith traditions, or more secular rational frameworks. This realization, that a satisfactory account of applied normative ethics calls for an anthropology—a substantive view of the good for the human person and the common good of the human community—I call the anthropological insight. Without this insight, appeals to the interests of shareholders or stakeholders have very little content. Before concluding, this chapter explores two important topics: (a) the nature of the common good, and (b) the relevance of “mediating institutions.” Under (a), I discuss the aspiration of “integral human development” emphasized in several faith-based traditions. It maintains that if we focus on the good of the whole person, body and soul, including the reaching out for relationships that whole persons need for their flourishing, the good of all (the common good) can be achieved. Under (b), I argue that the common good requires mediating institutions between the individual and society at large: the family, churches, schools, voluntary organizations, businesses, and local governments. These institutions foster and reinforce the social motivations that are essential to the pursuit of the common good. This chapter is an organic part of a larger work about the overall contribution of Kenneth Goodpaster to the field of applied ethics and is best read in the context of that larger work.
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Shulman, L. N. "Is anaplastic large cell lymphoma (ALCL) clinically distinct from diffuse large B cell lymphoma?" In Human Lymphoma: Clinical Implications of the REAL Classification, 225–31. London: Springer London, 1999. http://dx.doi.org/10.1007/978-1-4471-0857-3_39.
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Bassan, R., A. Rambaldi, E. Pogliani, G. Rossi, P. Fabris, S. Morandi, P. Casula, et al. "Preliminary Results of a Risk-Oriented Program for B-Lineage Adult Acute Lymphoblastic Leukemia (ALL): The Collaborative Italian Study 08/96." In Haematology and Blood Transfusion / Hämatologie und Bluttransfusion, 419–25. Berlin, Heidelberg: Springer Berlin Heidelberg, 2001. http://dx.doi.org/10.1007/978-3-642-18156-6_68.
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Loiseau, Claire, Rafael Gutiérrez-López, Bruno Mathieu, Boris K. Makanga, Christophe Paupy, Nil Rahola, and Anthony J. Cornel. "Diversity and Distribution of the Arthropod Vectors of the Gulf of Guinea Oceanic Islands." In Biodiversity of the Gulf of Guinea Oceanic Islands, 383–405. Cham: Springer International Publishing, 2022. http://dx.doi.org/10.1007/978-3-031-06153-0_15.
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AbstractThe known arthropod vector species on the Gulf of Guinea islands belong to orders Diptera and Ixodida. Among the Diptera, the family Culicidae (mosquitoes) has the most species, 34 (6 endemic), Ceratopogonidae has 13 (all in the genus Culicoides), Tabanidae has 6, and Simuliidae has 3 (1 endemic). Ixodida has only 4 species. Most vector species and associated diseases are shared with mainland Africa. Some of these include (1) the human malaria vector Anopheles coluzzii, (2) yellow fever and dengue vector Aedes aegypti, and (3) the spotted fever group rickettsiae and Q fever vector Amblyomma spp. However, there is a considerable lack of information on the natural cycles of many vector-borne diseases that might impact local fauna, for which there may be some endemic pathogen lineages. Increased trade by air and sea should compel authorities to remain vigilant, to keep unwanted vectors and diseases at bay. Entomological diversity data remains scarce for Annobón and for the forested interior of the islands, where future sampling efforts may uncover new endemic species.
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Callaghan, Madeleine. "‘All is done as I have told’." In Eternity in British Romantic Poetry, 23–58. Liverpool University Press, 2022. http://dx.doi.org/10.3828/liverpool/9781800856066.003.0002.
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Chapter one views eternity as the vital preoccupation of Blake’s work. In There is No Natural Religion, Blake asserts that ‘less than All cannot satisfy Man’ (‘The Argument’, There is No Natural Religion, [b], V. E p. 2) as his conception of eternity is of the ‘All’ that can be imagined without limits. Blake’s artistic career is devoted to exploring eternity’s potential. In love with ‘the Human Imagination: which is the Divine Vision & Fruition’ (Milton: A Poem II. 32 [35], 19, E, p. 130), Blake shows that to write eternity is the ultimate challenge to the poet’s vision. Blake’s version of eternity is personal and compelling: source hunting cannot explain his myth making. Blake’s chosen task is to make his reader see as he sees, and ‘open the Eternal Worlds’ (Jerusalem I. 5. 18 E, p. 147) before our eyes.
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"5 Osteomyelitis." In Management of Orthopaedic Infections, edited by Antonia F. Chen. New York, NY: Thieme Medical Publishers, Inc., 2021. http://dx.doi.org/10.1055/b-0041-181980.
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Osteomyelitis is a fascinating condition that can affect all parts of the human skeleton. It presents in several distinct ways, but all have varying degrees of inflammation, systemic ill health, bone death, and soft-tissue compromise. Understanding the components of the disease and the interplay between bacteria, biofilm formation, and the host response is critical to successful treatment. Recent advances in diagnostic methods, imaging, local delivery of antimicrobials, and bone reconstruction have greatly improved the outcome for many patients. Surgery remains central to the effective treatment of chronic osteomyelitis and many acute cases. Eradication of infection is largely dependent on the skill of the surgeon in identifying the areas of dead bone and removing them during surgery. Osteomyelitis is challenging and rewarding to treat, and most patients should enjoy prolonged disease-free periods or cure. Holistic care of the patient requires close collaborative working in a multidisciplinary team including physicians, surgeons, nurses, and therapists to achieve the best outcomes.
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Matthews, Michael D., and David M. Schnyer. "Human Performance Optimization." In Human Performance Optimization, 425–34. Oxford University Press, 2019. http://dx.doi.org/10.1093/oso/9780190455132.003.0019.
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This chapter summarizes and integrates the various approaches to optimizing human performance addressed in this book. Strategies for performance enhancement are evaluated across the three main domains of focus in this volume—physical, cognitive, and social. Moreover, for each domain, the authors offer suggestions for those that may be applied in the near term versus those that, while potentially useful, await further research and development. There are many steps that organizations might undertake at present to enhance individual and team performance. Challenges to achieving this goal include (a) establishing HPO as a salient organizational goal, (b) developing a strategy that effectively reaches all levels of an organization, and (c) designing an approach that is relevant and suitable to the needs of the organization. A unifying theme involves the criticality of ensuring that scientifically derived approaches to enhancing human performance meet stringent ethical guidelines before being implemented.
Conference papers on the topic "Human B-lineage ALL (B-ALL)"
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Lin, Shan, Roger T. Luo, Mark Wunderlich, Joseph J. Kaberlein, Ahmad Rayes, John Anastasi, Maureen M. O'Brien, James C. Mulloy, and Michael J. Thirman. "Abstract PR01: A novel MLL-AF4 in vivo model phenocopies t(4;11) pro-B ALL and reveals a lymphoid lineage bias of the fusion protein in human cells." In Abstracts: AACR Special Conference: Advances in Pediatric Cancer Research: From Mechanisms and Models to Treatment and Survivorship; November 9-12, 2015; Fort Lauderdale, Florida. American Association for Cancer Research, 2016. http://dx.doi.org/10.1158/1538-7445.pedca15-pr01.
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Payne, Kimberly J., Rui-Jun Su, Olivia L. Francis, Shannalee R. Martinez, Terrence Bennett, Keshav Arogyaswamy, Christopher L. Morris, and Sinisa Dovat. "Abstract 1347: A human-mouse xenograft model to study the role of TSLP in CRLF2d B-ALL." In Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL. American Association for Cancer Research, 2012. http://dx.doi.org/10.1158/1538-7445.am2012-1347.
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Su, Rui-jun, Olivia L. Francis, Shannalee R. Martinez, Ineavely Baez, Terry-Ann Milford, Christopher L. Morris, Ross O. Fisher, Xiao-Bing Zhang, Sinisa Dovat, and Kimberly J. Payne. "Abstract 5027: In vivo effects of TSLP in a human-mouse xenograft model of CRLF2 B-ALL." In Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC. American Association for Cancer Research, 2013. http://dx.doi.org/10.1158/1538-7445.am2013-5027.
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Levi, Dennis M., and Stanley A. Klein. "Equivalent blur in human vision." In OSA Annual Meeting. Washington, D.C.: Optica Publishing Group, 1987. http://dx.doi.org/10.1364/oam.1987.wt6.
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We measured thresholds for two-line resolution and for two-line separation discrimination in central and peripheral vision using Gaussian blurred lines. For both tasks and at all eccentricities the dependence of thresholds on stimulus blur can be characterized as follows: Th = [U* (1 + B s /B E )2])1/2, where Th is the threshold, U is the unblurred threshold, B S is the stimulus blur, and BE is the equivalent intrinsic blur of the visual system. When the stimulus blur B S is small, it has no influence on the thresholds; when it is larger than the equivalent intrinsic blur B E the threshold is proportional to the stimulus blur. B E is contrast invariant.
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Mellor, Edward W., R. Harrison, and Andy A. West. "A Component-Based Human Machine Interface System for Automotive Manufacturing Machines." In ASME 7th Biennial Conference on Engineering Systems Design and Analysis. ASMEDC, 2004. http://dx.doi.org/10.1115/esda2004-58368.
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This paper presents a novel approach for the configuration and runtime usage of user interfaces or Human Machine Interface (HMI) systems based on research being conducted at the Distributed Systems Group, Loughborough University. This research is investigating the replacement of conventional PLC/PC systems with a Component Based control approach suitable for the automotive engine manufacturing industry. HMI (operator interface) systems for production machines must effectively fully support an increasingly complex machine lifecycle involving engineering input from many globally distributed engineering partners. Current HMI Systems are standalone offering poor connectivity and requiring highly specialist skilled personnel to develop and maintain the systems. The goal of Component Based (C-B) systems is to compose machines from modular units with embedded intelligence. The “intelligence” has different functional domains, e.g. sequencing and interlocking logic, 3D virtual modeling, visualization, diagnostics, service and operating interfaces, etc. The underlying framework of the C-B paradigm is a common model system repository where all components are stored. This facilitates visibility of the system common model to all the globally distributed engineering partners involved in a given project. Within the C-B framework, HMI systems are composed from instances of reusable software templates that are targeted at specific user types. User targeted operator interfaces offer a common look and feel that improves usability. The machine’s configuration is achieved by populating a series of HMI templates to produce a complete machine HMI system. A thin-client architecture is used based on server/ client internet technologies that allow the machine HMI to be executed on any internet enabled computer using a standard web browser. It is possible to drive both the real machine and a simulated 3D virtual machine model via the HMI, enabling engineers to be trained on the operation of the HMI prior to the real machine being completed.
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Lodinger, Natalie, Keith Jones, Akbar Siami-Namin, and Ben Widlus. "Non-Experts' Perceptions Regarding the Severity of Different Cyber-Attack Consequences: Implications for Designing Warning Messages and Modeling Threats." In 13th International Conference on Applied Human Factors and Ergonomics (AHFE 2022). AHFE International, 2022. http://dx.doi.org/10.54941/ahfe1002212.
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Cyber-defenders must account for users’ perceptions of attack consequence severity. However, research has yet to investigate such perceptions of a wide range of cyber-attack consequences. Thus, we had users rate the severity of 50 cyber-attack consequences. We then analyzed those ratings to a) understand perceived severity for each consequence, and b) compare perceived severity across select consequences. Further, we grouped ratings into the STRIDE threat model categories and c) analyzed whether perceived severity varied across those categories. The current study’s results suggest not all consequences are perceived to be equally severe; likewise, not all STRIDE threat model categories are perceived to be equally severe. Implications for designing warning messages and modeling threats are discussed.
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Günzler, W. A., B. Wolf, and L. Flohé. "CHARACTERIZATION OF RECOMBINANT HUMAN SINGLE-CHAIN LOW MOLECULAR WEIGHT UROKINASE (RE-SC-LUK)." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643602.
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RE-SC-LUK obtained from recomoinant b. con Bacteria showed a molecular mass similar to that of recombinant two-chain LUK (RE-TC-LUK) as judged from SDS-PAGE. By “Western“ blot analysis immunoreactivity of RE-SC-LUK was observed with monoclonal antibodies directed against the B chain but not with those against the A1 chain of urokinase. N-terminal sequence analysis c RE-SC-LUK showed identity to the A, chain of RE-TC_LUK and provided evidence for its single-chain nature, i.e. integrity of the Lys-Ile bond which is split in TC-UK. In all other respects structural identity of RE-SC-LUK and RE-TC-LUK was demonstrated by fingerprinting of fragments. Similar to recombinant pro-urokinase (RE-SCU-PA), RE-SC-LUK exhibits only marginal amidolytic activity, which is greatly enhanced by treatment with plasmin, but considerable fibrinolytic activity in a fibrin agar plate test.Thus, RE-SC-LUK is characterized as a fragment (residues 136 -411) of RE-SCU-PA, which lacks the “growth factor” and “kringle” domains. Moreover further evidence is provided that a free N-terminus of the B chain is essential for amidolytic but not for fibrinolytic activity of urokinase in more complex systems.
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Bush, Benjamin, and Katherine Chastain. "Cardi B meets Chuck Taylors : Immersing high school students into the design process through a shoe design workshop." In 13th International Conference on Applied Human Factors and Ergonomics (AHFE 2022). AHFE International, 2022. http://dx.doi.org/10.54941/ahfe1001884.
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In the fall of 2020 a university recruiter and an industrial design faculty member met to engage and inform high school students through an hour and a half long workshop. Specifically, we wanted to target underrepresented people groups from within our state and give them a glimpse of what working in a creative profession might look like. As we started to develop the workshop we learned that we needed to strike a balance between three main criteria. We needed to reference practicing professional designers and share their experiences. We needed to champion a collaborative and iterative design processes. And we needed to make the content accessible and entertaining. The method by which we join and convey these criteria is through a shoe design workshop. Why shoes one may ask? Because all students have experience with footwear and all students have an option about their choice of fashion.From the very conception of the workshop we have held conversations with professional shoe designers on how to run this workshop. While industrial design faculty are well versed in the design process they frequently lack the real world experience of designing a shoe from idea to manufacturing and marketing. To compensate for a lack of knowledge we reach out to prominent shoe designers at Q4 Sports, Adidas, Cole Hann, and Fear of God. These designers stress conducting rigorous research and beginning any visual development using the lateral view. In addition, they gifted the workshop with the drawings of their most popular shoes so each student could use the same underlying framework that the professionals use. The second challenge is to champion the collaborative and iterative process. Sadly, the abundant mechanism of high school testing discourages conversations with peers and multiple correct answers. To boost collaboration we encourage students to support each workshop with the most recent information via social media. We allow them to use their phones during class so long that they add culturally relevant information to the existing framework. To encourage iteration we take the before mentioned conversations and collectively turn them into multiple visual concepts. And not only that, we reinforce collaboration by empowering students to tell the professor what concepts work and which ones do not.All the prep work comes down to choosing a topic of investigation that is entertaining, thought provoking, and relevant all while being able to be quickly translated into 2 dimensional shoe based artwork. Get it right and we will successfully introduce the next generation of students to the design profession. Get it wrong and become another ineffective outreach program that tries too hard. Now in our fifth iteration of the workshop, we wish to share our methodology as how we engage high school students with modular content that empowers them to learn the design process through the intersection of shoe wear and celebrity.
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Rudenko, Svetlana, and Mads Haahr. "Psychogeography with Jack B. Yeats Art Sounding Gallery: Augmented Reality Locative Experience for Blind People." In 13th International Conference on Applied Human Factors and Ergonomics (AHFE 2022). AHFE International, 2022. http://dx.doi.org/10.54941/ahfe1001639.
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Sensory Substitution Devices (SSDs) are a relatively novel concept, based on the idea of the multisensory brain. Research on synaesthesia and sensory pairings has revealed that sensory modalities of the brain are interconnected. Nature has demonstrated examples of people who have lost one sense, which has then been substituted by increased ability in another, for example the case of Daniel Kish who navigates like a bat (Burgess, 2021) by clicking of the tongue (echolocation principle). To find a methodology for translating information from one sense to another, or substitute one sense with another is the principle for all SSDs. A number of approaches to assistive technologies for different impairments have been developed, for example for blind people, such as the vOICe “seeing with sound” and EyeMusic Apps, which convert visual images and colours into sound. While most SSDs are focused on functionality to offer life assistance, such as for navigation, little or no work has been done to include the blind into the emotional world of Visual Arts, despite the fact that there are 45 million blind people in the world (Amir Amedi). In this paper, we present an audio GPS based walking app that presents a translation of the visual expression of artworks by sound/music to deliver the emotional content of the paintings to blind people. The music is composed for six artworks of Irish artist symbolist Jack B. Yeats (1871-1957), specifically reflecting on shapes, colours and emotional content of painting by composer experienced in audio-visual synchronisation via synaesthesia (Rudenko and Córdoba Serrano, 2017). The project is centred around the development of a new methodology for multisensory design (MSD) through the design, implementation, and evaluation of a locative art experience with Augmented Reality (AR), hosted by Haunted Planet Studios (director Mads Haahr).
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Kwon, Hyun Jung, Yujiang Xiang, Salam Rahmatalla, R. Timothy Marler, Karim Abdel-Malek, and Jasbir S. Arora. "Optimization-Based Digital Human Dynamics: Santos™ Walking Backwards." In ASME 2007 International Design Engineering Technical Conferences and Computers and Information in Engineering Conference. ASMEDC, 2007. http://dx.doi.org/10.1115/detc2007-35616.
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An objective of this study is to simulate the backward walking motion of a full-body digital human model. The model consists of 55 degree of freedom – 6 degrees of freedom for global translation and rotation and 49 degrees of freedom representing the kinematics of the entire body. The resultant action of all the muscles at a joint is represented by the torque for each degree of freedom. The torques and angles at a joint are treated as unknowns in the optimization problem. The B-spline interpolation is used to represent the time histories of the joint angles and the well-established robotics formulation of the Denavit-Hartenberg method is used for kinematics analysis of the mechanical system. The recursive Lagrangian formulation is used to develop the equations of motion, and was chosen because of its known computational efficiency. The backwards walking problem is formulated as a nonlinear optimization problem. The control points of the B-splines for the joint angle profiles are treated as the design variables. For the performance measure, total dynamic effort that is represented as the integral of the sum of the squares of all the joint torques is minimized using a sequential quadratic programming algorithm. The solution is simulated in the Santos™ environment. Results of the optimization problem are the torque and joint angle profiles. The torques at the key joints and the ground reaction forces are compared to those for the forward walk in order to study the differences between the two walking patterns. Simulation results are approximately validated with the experimental data which is motion captured in the VSR Lab at the University of Iowa.
Reports on the topic "Human B-lineage ALL (B-ALL)"
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Brzoska, Michael, Wuyi Omitoogun, and Elisabeth Sköns. The Human Security Case for Military Expenditure Reductions. Stockholm International Peace Research Institute, March 2022. http://dx.doi.org/10.55163/tmrz9944.
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Global military expenditure has reached record levels. At the same time, hundreds of millions of people face non-traditional ‘vital’ risks and threats to their security—threats to their lives, livelihoods and dignity. Accelerating climate change and growing loss of biodiversity add unprecedented urgency to investing in people’s security. The concept of human security, as explained in this paper, emphasizes the security of people without neglecting the security of states and state order. The human security approach stresses the necessity to balance the financial needs from all vital risks and threats, regardless of their cause. It logically leads to a reassessment of spending on the military. It also seriously considers the fear that reducing military expenditure will reduce the security of states, a major barrier to past international initiatives to reduce military expenditure. As a first step to initiate the rebalancing, this paper proposes three priority fields of activity to free resources from military spending: (a) arms control and disarmament negotiations and agreements; (b) sector-wide security sector reform for conflict prevention; and (c) financial responsibility in military expenditure and arms procurement. These can be taken without impairing the security of states and state order. If successful, these steps would remove barriers to further military expenditure reductions to improve the human condition in an increasingly dangerous Anthropocene.
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Ficht, Thomas, Gary Splitter, Menachem Banai, and Menachem Davidson. Characterization of B. Melinensis REV 1 Attenuated Mutants. United States Department of Agriculture, December 2000. http://dx.doi.org/10.32747/2000.7580667.bard.
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Brucella Mutagenesis (TAMU) The working hypothesis for this study was that survival of Brucella vaccines was directly related to their persistence in the host. This premise is based on previously published work detailing the survival of the currently employed vaccine strains S19 and Rev 1. The approach employed signature-tagged mutagenesis to construct mutants interrupted in individual genes, and the mouse model to identify mutants with attenuated virulence/survival. Intracellular survival in macrophages is the key to both reproductive disease in ruminants and reticuloendothelial disease observed in most other species. Therefore, the mouse model permitted selection of mutants of reduced intracellular survival that would limit their ability to cause reproductive disease in ruminants. Several classes of mutants were expected. Colonization/invasion requires gene products that enhance host-agent interaction or increase resistance to antibacterial activity in macrophages. The establishment of chronic infection requires gene products necessary for intracellular bacterial growth. Maintenance of chronic infection requires gene products that sustain a low-level metabolism during periods characterized little or no growth (1, 2). Of these mutants, the latter group was of greatest interest with regard to our originally stated premise. However, the results obtained do not necessarily support a simplistic model of vaccine efficacy, i.e., long-survival of vaccine strains provides better immunity. Our conclusion can only be that optimal vaccines will only be developed with a thorough understanding of host agent interaction, and will be preferable to the use of fortuitous isolates of unknown genetic background. Each mutant could be distinguished from among a group of mutants by PCR amplification of the signature tag (5). This approach permitted infection of mice with pools of different mutants (including the parental wild-type as a control) and identified 40 mutants with apparently defective survival characteristics that were tentatively assigned to three distinct classes or groups. Group I (n=13) contained organisms that exhibited reduced survival at two weeks post-infection. Organisms in this group were recovered at normal levels by eight weeks and were not studied further, since they may persist in the host. Group II (n=11) contained organisms that were reduced by 2 weeks post infection and remained at reduced levels at eight weeks post-infection. Group III (n=16) contained mutants that were normal at two weeks, but recovered at reduced levels at eight weeks. A subset of these mutants (n= 15) was confirmed to be attenuated in mixed infections (1:1) with the parental wild-type. One of these mutants was eliminated from consideration due to a reduced growth rate in vitro that may account for its apparent growth defect in the mouse model. Although the original plan involved construction of the mutant bank in B. melitensis Rev 1 the low transformability of this strain, prevented accumulation of the necessary number of mutants. In addition, the probability that Rev 1 already carries one genetic defect increases the likelihood that a second defect will severely compromise the survival of this organism. Once key genes have been identified, it is relatively easy to prepare the appropriate genetic constructs (knockouts) lacking these genes in B. melitensis Rev 1 or any other genetic background. The construction of "designer" vaccines is expected to improve immune protection resulting from minor sequence variation corresponding to geographically distinct isolates or to design vaccines for use in specific hosts. A.2 Mouse Model of Brucella Infection (UWISC) Interferon regulatory factor-1-deficient (IRF-1-/- mice have diverse immunodeficient phenotypes that are necessary for conferring proper immune protection to intracellular bacterial infection, such as a 90% reduction of CD8+ T cells, functionally impaired NK cells, as well as a deficiency in iNOS and IL-12p40 induction. Interestingly, IRF-1-/- mice infected with diverse Brucella abortus strains reacted differently in a death and survival manner depending on the dose of injection and the level of virulence. Notably, 50% of IRF-1-/- mice intraperitoneally infected with a sublethal dose in C57BL/6 mice, i.e., 5 x 105 CFU of virulent S2308 or the attenuated vaccine S19, died at 10 and 20 days post-infection, respectively. Interestingly, the same dose of RB51, an attenuated new vaccine strain, did not induce the death of IRF-1-/- mice for the 4 weeks of infection. IRF-1-/- mice infected with four more other genetically manipulated S2308 mutants at 5 x 105 CFU also reacted in a death or survival manner depending on the level of virulence. Splenic CFU from C57BL/6 mice infected with 5 x 105 CFU of S2308, S19, or RB51, as well as four different S2308 mutants supports the finding that reduced virulence correlates with survival Of IRF-1-/- mice. Therefore, these results suggest that IRF-1 regulation of multi-gene transcription plays a crucial role in controlling B. abortus infection, and IRF-1 mice could be used as an animal model to determine the degree of B. abortus virulence by examining death or survival. A3 Diagnostic Tests for Detection of B. melitensis Rev 1 (Kimron) In this project we developed an effective PCR tool that can distinguish between Rev1 field isolates and B. melitensis virulent field strains. This has allowed, for the first time, to monitor epidemiological outbreaks of Rev1 infection in vaccinated flocks and to clearly demonstrate horizontal transfer of the strain from vaccinated ewes to unvaccinated ones. Moreover, two human isolates were characterized as Rev1 isolates implying the risk of use of improperly controlled lots of the vaccine in the national campaign. Since atypical B. melitensis biotype 1 strains have been characterized in Israel, the PCR technique has unequivocally demonstrated that strain Rev1 has not diverted into a virulent mutant. In addition, we could demonstrate that very likely a new prototype biotype 1 strain has evolved in the Middle East compared to the classical strain 16M. All the Israeli field strains have been shown to differ from strain 16M in the PstI digestion profile of the omp2a gene sequence suggesting that the local strains were possibly developed as a separate branch of B. melitensis. Should this be confirmed these data suggest that the Rev1 vaccine may not be an optimal vaccine strain for the Israeli flocks as it shares the same omp2 PstI digestion profile as strain 16M.
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Gillor, Osnat, Stefan Wuertz, Karen Shapiro, Nirit Bernstein, Woutrina Miller, Patricia Conrad, and Moshe Herzberg. Science-Based Monitoring for Produce Safety: Comparing Indicators and Pathogens in Water, Soil, and Crops. United States Department of Agriculture, May 2013. http://dx.doi.org/10.32747/2013.7613884.bard.
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Using treated wastewater (TWW) for crop irrigation represents an important opportunity for ensuring adequate food production in light of growing freshwater scarcity worldwide. However, the environmentally sustainable approach of using TWW for irrigation can lead to contamination of produce with fecal pathogens that may remain in treated water. The overall goal of this research was to evaluate the correlation between the presence of fecal indicator bacteria (FIB) and that of a suite of human pathogens in TWW, the irrigated soil, and crops. Field experiments were conducted to compare secondary and tertiary TWW with dechlorinated tap water for irrigation of tomatoes, a typical commercial crop, in Israel, a semi-arid country. Human pathogens including bacteria (Salmonella), protozoa (Cryptosporidiumand Giardia), and viruses (Adenovirus [AV Types A, B, C & 40/41] and Enterovirus [EV71 subtypes]) were monitored in two field trials using a combination of microscopic, cultivation-based, and molecular (qPCR) techniques. Results from the field trials indicate that microbial contamination on the surface of tomatoes did not appear to be associated with the source of irrigated waters; FIB contamination was not statistically different on tomatoes irrigated with TWW as compared to tomatoes irrigated with potable water. In fact, Indicator bacteria testing did not predict the presence of pathogens in any of the matrices tested. High concentrations of FIB were detected in water and on tomato surfaces from all irrigation treatment schemes, while pathogen contamination on tomato surfaces (Cryptosporidiumand Salmonella) was only detected on crops irrigated with TWW. These results suggest that regular monitoring for pathogens should take place to accurately detect presence of harmful microorganisms that could threaten consumer safety. A notable result from our study is that the large numbers of FIB in the water did not appear to lead to FIB accumulation in the soil. With the exception of two samples, E. coli that was present at 10³ to 10⁴ cells/100 mL in the water, was not detected in the soil. Other bacterial targets associated with the enteric environment (e. g., Proteusspp.) as well as protozoal pathogens were detected in the TWW, but not in the soil. These findings suggest that significant microbial transfer to the soil from TWW did not occur in this study. The pattern of FIB contamination on the surfaces of tomatoes was the same for all treatment types, and showed a temporal effect with more contamination detected as the duration of the field trial increased. An important observation revealed that water quality dramatically deteriorated between the time of its release from the wastewater treatment plant and the time it was utilized for irrigation, highlighting the importance of performing water quality testing throughout the growing season at the cultivation site.
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Hall, Mark, and Neil Price. Medieval Scotland: A Future for its Past. Society of Antiquaries of Scotland, September 2012. http://dx.doi.org/10.9750/scarf.09.2012.165.
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The main recommendations of the panel report can be summarised under five key headings. Underpinning all five areas is the recognition that human narratives remain crucial for ensuring the widest access to our shared past. There is no wish to see political and economic narratives abandoned but the need is recognised for there to be an expansion to more social narratives to fully explore the potential of the diverse evidence base. The questions that can be asked are here framed in a national context but they need to be supported and improved a) by the development of regional research frameworks, and b) by an enhanced study of Scotland’s international context through time. 1. From North Britain to the Idea of Scotland: Understanding why, where and how ‘Scotland’ emerges provides a focal point of research. Investigating state formation requires work from Medieval Scotland: a future for its past ii a variety of sources, exploring the relationships between centres of consumption - royal, ecclesiastical and urban - and their hinterlands. Working from site-specific work to regional analysis, researchers can explore how what would become ‘Scotland’ came to be, and whence sprang its inspiration. 2. Lifestyles and Living Spaces: Holistic approaches to exploring medieval settlement should be promoted, combining landscape studies with artefactual, environmental, and documentary work. Understanding the role of individual sites within wider local, regional and national settlement systems should be promoted, and chronological frameworks developed to chart the changing nature of Medieval settlement. 3. Mentalities: The holistic understanding of medieval belief (particularly, but not exclusively, in its early medieval or early historic phase) needs to broaden its contextual understanding with reference to prehistoric or inherited belief systems and frames of reference. Collaborative approaches should draw on international parallels and analogues in pursuit of defining and contrasting local or regional belief systems through integrated studies of portable material culture, monumentality and landscape. 4. Empowerment: Revisiting museum collections and renewing the study of newly retrieved artefacts is vital to a broader understanding of the dynamics of writing within society. Text needs to be seen less as a metaphor and more as a technological and social innovation in material culture which will help the understanding of it as an experienced, imaginatively rich reality of life. In archaeological terms, the study of the relatively neglected cultural areas of sensory perception, memory, learning and play needs to be promoted to enrich the understanding of past social behaviours. 5. Parameters: Multi-disciplinary, collaborative, and cross-sector approaches should be encouraged in order to release the research potential of all sectors of archaeology. Creative solutions should be sought to the challenges of transmitting the importance of archaeological work and conserving the resource for current and future research.
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Malkinson, Mertyn, Irit Davidson, Moshe Kotler, and Richard L. Witter. Epidemiology of Avian Leukosis Virus-subtype J Infection in Broiler Breeder Flocks of Poultry and its Eradication from Pedigree Breeding Stock. United States Department of Agriculture, March 2003. http://dx.doi.org/10.32747/2003.7586459.bard.
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Objectives 1. Establish diagnostic procedures to identify tolerant carrier birds based on a) Isolation of ALV-J from blood, b) Detection of group-specific antigen in cloacal swabs and egg albumen. Application of these procedures to broiler breeder flocks with the purpose of removing virus positive birds from the breeding program. 2. Survey the AL V-J infection status of foundation lines to estimate the feasibility of the eradication program 3. Investigate virus transmission through the embryonated egg (vertical) and between chicks in the early post-hatch period (horizontal). Establish a model for limiting horizontal spread by analyzing parameters operative in the hatchery and brooder house. 4. Compare the pathogenicity of AL V-J isolates for broiler chickens. 5. Determine whether AL V-J poses a human health hazard by examining its replication in mammalian and human cells. Revisions. The: eradication objective had to be terminated in the second year following the closing down of the Poultry Breeders Union (PBU) in Israel. This meant that their foundation flocks ceased to be available for selection. Instead, the following topics were investigated: a) Comparison of commercial breeding flocks with and without myeloid leukosis (matched controls) for viremia and serum antibody levels. b) Pathogenicity of Israeli isolates for turkey poults. c) Improvement of a diagnostic ELISA kit for measuring ALV-J antibodies Background. ALV-J, a novel subgroup of the avian leukosis virus family, was first isolated in 1988 from broiler breeders presenting myeloid leukosis (ML). The extent of its spread among commercial breeding flocks was not appreciated until the disease appeared in the USA in 1994 when it affected several major breeding companies almost simultaneously. In Israel, ML was diagnosed in 1996 and was traced to grandparent flocks imported in 1994-5, and by 1997-8, ML was present in one third of the commercial breeding flocks It was then realized that ALV-J transmission was following a similar pattern to that of other exogenous ALVs but because of its unusual genetic composition, the virus was able to establish an extended tolerant state in infected birds. Although losses from ML in affected flocks were somewhat higher than normal, both immunosuppression and depressed growth rates were encountered in affected broiler flocks and affected their profitability. Conclusions. As a result of the contraction in the number of international primary broiler breeders and exchange of male and female lines among them, ALV-J contamination of broiler breeder flocks affected the broiler industry worldwide within a short time span. The Israeli national breeding company (PBU) played out this scenario and presented us with an opportunity to apply existing information to contain the virus. This BARD project, based on the Israeli experience and with the aid of the ADOL collaborative effort, has managed to offer solutions for identifying and eliminating infected birds based on exhaustive virological and serological tests. The analysis of factors that determine the efficiency of horizontal transmission of virus in the hatchery resulted in the workable solution of raising young chicks in small groups through the brooder period. These results were made available to primary breeders as a strategy for reducing viral transmission. Based on phylogenetic analysis of selected Israeli ALV-J isolates, these could be divided into two groups that reflected the countries of origin of the grandparent stock. Implications. The availability of a simple and reliable means of screening day old chicks for vertical transmission is highly desirable in countries that rely on imported breeding stock for their broiler industry. The possibility that AL V-J may be transmitted to human consumers of broiler meat was discounted experimentally.
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Ohad, Itzhak, and Himadri Pakrasi. Role of Cytochrome B559 in Photoinhibition. United States Department of Agriculture, December 1995. http://dx.doi.org/10.32747/1995.7613031.bard.
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The aim of this research project was to obtain information on the role of the cytochrome b559 in the function of Photosystem-II (PSII) with special emphasis on the light induced photo inactivation of PSII and turnover of the photochemical reaction center II protein subunit RCII-D1. The major goals of this project were: 1) Isolation and sequencing of the Chlamydomonas chloroplast psbE and psbF genes encoding the cytochrome b559 a and b subunits respectively; 2) Generation of site directed mutants and testing the effect of such mutation on the function of PSII under various light conditions; 3) To obtain further information on the mechanism of the light induced degradation and replacement of the PSII core proteins. This information shall serve as a basis for the understanding of the role of the cytochrome b559 in the process of photoinhibition and recovery of photosynthetic activity as well as during low light induced turnover of the D1 protein. Unlike in other organisms in which the psbE and psbF genes encoding the a and b subunits of cytochrome b559, are part of an operon which also includes the psbL and psbJ genes, in Chlamydomonas these genes are transcribed from different regions of the chloroplast chromosome. The charge distribution of the derived amino-acid sequences of psbE and psbF gene products differs from that of the corresponding genes in other organisms as far as the rule of "positive charge in" is concerned relative to the process of the polypeptide insertion in the thylakoid membrane. However, the sum of the charges of both subunits corresponds to the above rule possibly indicating co-insertion of both subunits in the process of cytochrome b559 assembly. A plasmid designed for the introduction of site-specific mutations into the psbF gene of C. reinhardtii. was constructed. The vector consists of a DNA fragment from the chromosome of C. reinhardtii which spans the region of the psbF gene, upstream of which the spectinomycin-resistance-conferring aadA cassette was inserted. This vector was successfully used to transform wild type C. reinhardtii cells. The spectinomycin resistant strain thus obtained can grow autotrophically and does not show significant changes as compared to the wild-type strain in PSII activity. The following mutations have been introduced in the psbF gene: H23M; H23Y; W19L and W19. The replacement of H23 involved in the heme binding to M and Y was meant to permit heme binding but eventually alter some or all of the electron transport properties of the mutated cytochrome. Tryptophane W19, a strictly conserved residue, is proximal to the heme and may interact with the tetrapyrole ring. Therefore its replacement may effect the heme properties. A change to tyrosine may have a lesser affect on the potential or electron transfer rate while a replacement of W19 by leucine is meant to introduce a more prominent disturbance in these parameters. Two of the mutants, FW19L and FH23M have segregated already and are homoplasmic. The rest are still grown under selection conditions until complete segregation will be obtained. All mutants contain assembled and functional PSII exhibiting an increased sensitivity of PSII to the light. Work is still in progress for the detailed characterization of the mutants PSII properties. A tobacco mutant, S6, obtained by Maliga and coworkers harboring the F26S mutation in the b subunit was made available to us and was characterized. Measurements of PSII charge separation and recombination, polypeptide content and electron flow indicates that this mutation indeed results in light sensitivity. Presently further work is in progress in the detailed characterization of the properties of all the above mutants. Information was obtained demonstrating that photoinactivation of PSII in vivo initiates a series of progressive changes in the properties of RCII which result in an irreversible modification of the RCII-D1 protein leading to its degradation and replacement. The cleavage process of the modified RCII-D1 protein is regulated by the occupancy of the QB site of RCII by plastoquinone. Newly synthesized D1 protein is not accumulated in a stable form unless integrated in reassembled RCII. Thus the degradation of the irreversibly modified RCII-D1 protein is essential for the recovery process. The light induced degradation of the RCII-D1 protein is rapid in mutants lacking the pD1 processing protease such as in the LF-1 mutant of the unicellular alga Scenedesmus obliquus. In this case the Mn binding site of PSII is abolished, the water oxidation process is inhibited and harmful cation radicals are formed following light induced electron flow in PSII. In such mutants photo-inactivation of PSII is rapid, it is not protected by ligands binding at the QB site and the degradation of the inactivated RCII-D1 occurs rapidly also in the dark. Furthermore the degraded D1 protein can be replaced in the dark in absence of light driven redox controlled reactions. The replacement of the RCII-D1 protein involves the de novo synthesis of the precursor protein, pD1, and its processing at the C-terminus end by an unknown processing protease. In the frame of this work, a gene previously isolated and sequenced by Dr. Pakrasi's group has been identified as encoding the RCII-pD1 C-terminus processing protease in the cyanobacterium Synechocystis sp. PCC 6803. The deduced sequence of the ctpA protein shows significant similarity to the bovine, human and insect interphotoreceptor retinoid-binding proteins. Results obtained using C. reinhardtii cells exposes to low light or series of single turnover light flashes have been also obtained indicating that the process of RCII-D1 protein turnover under non-photoinactivating conditions (low light) may be related to charge recombination in RCII due to back electron flow from the semiquinone QB- to the oxidised S2,3 states of the Mn cluster involved in the water oxidation process.
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Ahnert, Markus, Mandy Arndt, Matthias Barth, Stephan Beil, Hilmar Börnick, Mareike Braeckevelt, Joachim Fauler, et al. MikroModell Entwicklung eines Stoffflussmodells und Leitfadens zur Emissionsminderung von Mikroschadstoffen im Hinblick auf die Wasserqualität. Gunda Röstel, Prof. Dr. Peter Krebs, September 2021. http://dx.doi.org/10.25368/2021.68.
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Das Forschungsvorhaben “Entwicklung eines Stoffflussmodells und Leitfadens zur Emis-sionsminderung von Mikroschadstoffen im Hinblick auf die Wasserqualität“ (MikroModell) wurde im Zeitraum von Oktober 2015 bis Juni 2020 von der Deutschen Bundesstiftung Umwelt, dem Sächsischen Staatsministerium für Umwelt und Landwirtschaft (heute Sächsisches Staatsministerium für Energie, Klimaschutz, Umwelt und Landwirtschaft) sowie der Gelsenwasser AG gefördert. An dem interdisziplinären Projektkonsortium waren ne-ben den Betreibern der Abwassersysteme und -anlagen in Dresden, Chemnitz und Plauen Wissenschaftler:innen aus den Bereichen der Siedlungswasserwirtschaft, Hydrobiologie, Ökotoxikologie, Wasserchemie, Umweltökonomie, Pharmakologie an der Technischen Universität Dresden sowie des Wirtschafts- und Regulierungsrechts an der Technischen Univer-sität Bergakademie Freiberg beteiligt. In MikroModell wurde anhand unterschiedlich dicht besiedelter sächsischer Regionen untersucht, welche Verbesserungen der Gewässerqualität durch technologische Maßnahmen im Abwassersystem, durch Reduktionsmaßnahmen an der Quelle und in der Anwendung, durch rechtliche Steuerungsmaßnahmen auf EU-, Bundes- und Landesebene sowie durch Aktivitäten im Rahmen einer regional fokussierten Öffentlichkeitsarbeit erzielt werden können, um so eine effiziente und nachhaltige Entwicklung zu befördern. Dazu wurden sowohl Substanzen der Liste prioritärer Stoffe als auch weitere Spurenstoffe an Hand verfügbarer Umweltqualitätsnormen (UQN) bewertet. Der Bericht ist in zwei Teilen organisiert. Teil A beinhaltet den Handlungsleitfaden und richtet sich an Entscheidungsträger und Betreiberorganisationen, beschreibt also die praxisrelevanten Folgerungen aus den Untersuchungen. In Teil B werden die wissenschaftlichen Grundlagen und die Untersuchungsmethoden detailliert erläutert sowie ausgewählte Ergebnisse diskutiert. In Teil A wird eine systematische Vorgehensweise zur Bewertung der Relevanz von ab-wasserbürtigen Mikroschadstoffen und zur Entscheidungsfindung bzgl. Optionen zur Reduktion der Gewässerbelastung mit Mikroschadstoffen vorgestellt (Kapitel A-2). Die Durchführungsempfehlung ist in einem Prozessschema zusammengefasst, das die Maß-nahmenfindung als gemeinsamen Weg von Aufgabenträgern und Behörden beschreibt. Grundlage für die Bewertung der aktuellen Situation bildet die Auswertung der Gewäs-sergütedaten des LfULG (2009 – 2018) und zweier 21-Tage Monitoringkampagnen an den Kläranlagen-Standorten Dresden, Chemnitz und Plauen. IX Die Auswirkungen von Maßnahmen im technologischen Bereich und an der Quelle werden mittels Stoffflussmodellierung aufgezeigt. In Teil A werden dazu Simulationsergebnisse für Dresden, Chemnitz und Plauen herangezogen, die zeigen, dass sich für unter-schiedliche Einzugsgebiete und Stoffe unterschiedliche Maßnahmen als effektiv erweisen (Kapitel A-3). Darüber hinaus erweist sich auch die Definition der Zielgrößen als maßge-bend für die Priorisierung von Maßnahmen. Es gilt den Diskurs dazu anzustoßen. Neben konkreten technologischen Handlungsoptionen und Bewirtschaftungsansätzen an der Quelle werden auch rechtliche Handlungsoptionen in die Betrachtung miteinbezogen (Kapitel A-4). Um die Verwendungen und den Eintrag von Mikroschadstoffen aus Pflan-zenschutzmitteln, Arzneimitteln sowie Industrie- und Haushaltschemikalien mittel- und langfristig zu vermindern, wurden konkrete Empfehlungen zur Anwendung bzw. zu Anpassungen in den Bereichen des Wasser-, Arzneimittel- (Human- & Tierarzneimittelrecht), Chemikalien-, Düngemittel-, Pflanzenschutz- und Biozidrechts herausgearbeitet. Schließlich werden flankierende Aktivitäten zur Information ausgewählter Multiplikatoren und zur Aufklärung der Öffentlichkeit als unerlässlich erkannt und beschrieben (Kapitel A-5). Neben Maßnahmen zur Sensibilisierung der Bürger wurden insbesondere Kommunikationsveranstaltungen mit Ärzten und Apothekern durchgeführt. Dabei wurde zielgerichtet ein Verständnis für den nachhaltigen Einsatz und die gesicherte Entsorgung von Arzneimitteln vermittelt und allgemein das Bewusstsein geschärft, dass verschriebene Wirksubstanzen als solche oder metabolisiert/transformiert im Abwasser und ggf. im Gewässer wiederzufinden sind. Die Zusammenarbeit mit der Ärzteschaft erscheint nicht nur als zentraler Baustein zukunftsgerichteten Handelns wichtig, sondern wird auch als erfolgsversprechend angesehen. Der in Teil A vorgestellte Handlungsleitfaden vermittelt letztlich keine absolute Priorisierung von Handlungsoptionen, da sich für unterschiedliche Zielsetzungen und unter-schiedliche Bedingungen eine veränderte Priorisierung ergibt. Es wird aber der Weg hin zur Identifikation der unter den gegebenen Bedingungen besten Handlungsoption bzw. einer erfolgsversprechenden Kombination von Handlungsoptionen aufgezeigt. Dieses systematische Vorgehen wurde zwar am Beispiel von drei Pilotgebieten durchgespielt und für Sachsen flächendeckend aufbereitet, ist aber letztlich übertragbar auf andere Gebiete Deutschlands oder Europas. In Teil B werden die wissenschaftlichen Grundlagen sowie ausgewählte Ergebnisse des Projektes erläutert – sofern sie nicht schon in Teil A, den Handlungsleitfaden, eingeflossen sind (siehe den rechtlichen Handlungsrahmen sowie die Empfehlungen für die Öffentlich-keitsarbeit). Teil B ist in drei Kapitel unterteilt: Monitoring und Untersuchungen vor Ort (Kapitel B-1), Reduktionsmaßnahmen im Umgang mit Mikroschadstoffen (Kapitel B-2), Er-stellung und Kalibrierung des Stoffflussmodells sowie die Entwicklungsszenarien zur exemplarischen Anwendung des Modells (Kapitel B-3). X Kapitel B-1 umfasst das methodische Vorgehen zur Auswahl der Substanzen mit erhöhter Priorität an allen drei Standorten sowie eine Bewertung der Entwicklungstrends der Verschreibungsmengen für verschiedene Arzneistoffgruppen. Die Ergebnisse der vier Moni-toringkampagnen, die mit kombinierten chemischen und ökotoxikologischen Analysen verbunden waren, werden zusammengefasst und ergänzende Untersuchungen zur Bewertung der Mischwasserentlastungen erläutert. Die in Kapitel B-2 beschriebenen Untersuchungen zu Reduktionsmaßnahmen im Umgang mit Mikroschadstoffen beinhalten neben einer Übersicht zu den Kosten einer 4. Reinigungs-stufe die Bewertung verschiedener Verfahren zur Elimination von Spurenstoffen (Pulverak-tivkohle, Ozonierung und Sandfiltration) auf Grundlage von Laborversuchen. Zudem werden die Einträge industrieller und gewerblicher Einleiter in die Kanalnetze der Modellre-gionen und schließlich die Möglichkeiten von Reduktions- und Vermeidungsmaßnahmen auf Grundlage einer Literaturrecherche sowie von Experteninterviews mit verschiedenen Akteuren und Multiplikatoren bewertet. In Kapitel B-3 werden die Methoden zur Verschneidung der verschiedensten verfügbaren Informationen zur Stoffflussmodellierung beschrieben. Die verfügbaren, auf 186 vierstellige Postleitzahlbereiche bezogenen Daten zur Medikamentenverschreibung werden mit den 429 Gemeinden verschnitten, die Bevölkerung wird den Kläranlagen zugeordnet, die Kläranlagenabläufe müssen an den Fließgewässern verortet werden und sämtliche vom Land verfügbaren Informationen von Abfluss- und Qualitätsmessstellen müssen derart prozessiert werden, dass sie mit den modellierten Kläranlagenablaufwerten sinnvoll kombiniert werden können. Schließlich erfolgt die Kalibrierung und Validierung sowie die Anwendung des Stoffflussmodells zur Untersuchung von Entwicklungsszenarien und Handlungsoptionen. Die methodischen Grundlagen sind damit für eine erweiterte Anwendung und eine Übertragung auf andere Gebiete gegeben.
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Adams, Alexandra, Robert Byron, Bruce Maxwell, Susan Higgins, Margaret Eggers, Lori Byron, and Cathy Whitlock. Climate change and human health in Montana: a special report of the Montana Climate Assessment. Montana State University, December 2020. http://dx.doi.org/10.15788/c2h22021.
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The purpose of this assessment is to a) present understandable, science-based, Montana-specific information about the impacts of climate change on the health of Montanans; and b) describe how our healthcare providers, state leaders, communities, and individuals can best prepare for and reduce those impacts in the coming decades. This assessment draws from, and is an extension to, the 2017 Montana Climate Assessment (MCA1) (Whitlock et al. 2017), which provides the first detailed analysis of expected impacts to Montana’s water, forests, and agriculture from climate change. MCA explains historical, current, and prospective climate trends for the state based on the best-available science. The 2017 Montana Climate Assessment did not address the impact of climate change on the health of Montanans. This special report of the MCA fills that important knowledge gap; it represents a collaboration between climate scientists and Montana’s healthcare community and is intended to help Montanans minimize the impacts of climate on their health.
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Cytryn, Eddie, Mark R. Liles, and Omer Frenkel. Mining multidrug-resistant desert soil bacteria for biocontrol activity and biologically-active compounds. United States Department of Agriculture, January 2014. http://dx.doi.org/10.32747/2014.7598174.bard.
Full textAbstract:
Control of agro-associated pathogens is becoming increasingly difficult due to increased resistance and mounting restrictions on chemical pesticides and antibiotics. Likewise, in veterinary and human environments, there is increasing resistance of pathogens to currently available antibiotics requiring discovery of novel antibiotic compounds. These drawbacks necessitate discovery and application of microorganisms that can be used as biocontrol agents (BCAs) and the isolation of novel biologically-active compounds. This highly-synergistic one year project implemented an innovative pipeline aimed at detecting BCAs and associated biologically-active compounds, which included: (A) isolation of multidrug-resistant desert soil bacteria and root-associated bacteria from medicinal plants; (B) invitro screening of bacterial isolates against known plant, animal and human pathogens; (C) nextgeneration sequencing of isolates that displayed antagonistic activity against at least one of the model pathogens and (D) in-planta screening of promising BCAs in a model bean-Sclerotiumrolfsii system. The BCA genome data were examined for presence of: i) secondary metabolite encoding genes potentially linked to the anti-pathogenic activity of the isolates; and ii) rhizosphere competence-associated genes, associated with the capacity of microorganisms to successfully inhabit plant roots, and a prerequisite for the success of a soil amended BCA. Altogether, 56 phylogenetically-diverse isolates with bioactivity against bacterial, oomycete and fungal plant pathogens were identified. These strains were sent to Auburn University where bioassays against a panel of animal and human pathogens (including multi-drug resistant pathogenic strains such as A. baumannii 3806) were conducted. Nineteen isolates that showed substantial antagonistic activity against at least one of the screened pathogens were sequenced, assembled and subjected to bioinformatics analyses aimed at identifying secondary metabolite-encoding and rhizosphere competence-associated genes. The genome size of the bacteria ranged from 3.77 to 9.85 Mbp. All of the genomes were characterized by a plethora of secondary metabolite encoding genes including non-ribosomal peptide synthase, polyketidesynthases, lantipeptides, bacteriocins, terpenes and siderophores. While some of these genes were highly similar to documented genes, many were unique and therefore may encode for novel antagonistic compounds. Comparative genomic analysis of root-associated isolates with similar strains not isolated from root environments revealed genes encoding for several rhizospherecompetence- associated traits including urea utilization, chitin degradation, plant cell polymerdegradation, biofilm formation, mechanisms for iron, phosphorus and sulfur acquisition and antibiotic resistance. Our labs are currently writing a continuation of this feasibility study that proposes a unique pipeline for the detection of BCAs and biopesticides that can be used against phytopathogens. It will combine i) metabolomic screening of strains from our collection that contain unique secondary metabolite-encoding genes, in order to isolate novel antimicrobial compounds; ii) model plant-based experiments to assess the antagonistic capacities of selected BCAs toward selected phytopathogens; and iii) an innovative next-generation-sequencing based method to monitor the relative abundance and distribution of selected BCAs in field experiments in order to assess their persistence in natural agro-environments. We believe that this integrated approach will enable development of novel strains and compounds that can be used in large-scale operations.
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McCarthy, Noel, Eileen Taylor, Martin Maiden, Alison Cody, Melissa Jansen van Rensburg, Margaret Varga, Sophie Hedges, et al. Enhanced molecular-based (MLST/whole genome) surveillance and source attribution of Campylobacter infections in the UK. Food Standards Agency, July 2021. http://dx.doi.org/10.46756/sci.fsa.ksj135.
Full textAbstract:
This human campylobacteriosis sentinel surveillance project was based at two sites in Oxfordshire and North East England chosen (i) to be representative of the English population on the Office for National Statistics urban-rural classification and (ii) to provide continuity with genetic surveillance started in Oxfordshire in October 2003. Between October 2015 and September 2018 epidemiological questionnaires and genome sequencing of isolates from human cases was accompanied by sampling and genome sequencing of isolates from possible food animal sources. The principal aim was to estimate the contributions of the main sources of human infection and to identify any changes over time. An extension to the project focussed on antimicrobial resistance in study isolates and older archived isolates. These older isolates were from earlier years at the Oxfordshire site and the earliest available coherent set of isolates from the national archive at Public Health England (1997/8). The aim of this additional work was to analyse the emergence of the antimicrobial resistance that is now present among human isolates and to describe and compare antimicrobial resistance in recent food animal isolates. Having identified the presence of bias in population genetic attribution, and that this was not addressed in the published literature, this study developed an approach to adjust for bias in population genetic attribution, and an alternative approach to attribution using sentinel types. Using these approaches the study estimated that approximately 70% of Campylobacter jejuni and just under 50% of C. coli infection in our sample was linked to the chicken source and that this was relatively stable over time. Ruminants were identified as the second most common source for C. jejuni and the most common for C. coli where there was also some evidence for pig as a source although less common than ruminant or chicken. These genomic attributions of themselves make no inference on routes of transmission. However, those infected with isolates genetically typical of chicken origin were substantially more likely to have eaten chicken than those infected with ruminant types. Consumption of lamb’s liver was very strongly associated with infection by a strain genetically typical of a ruminant source. These findings support consumption of these foods as being important in the transmission of these infections and highlight a potentially important role for lamb’s liver consumption as a source of Campylobacter infection. Antimicrobial resistance was predicted from genomic data using a pipeline validated by Public Health England and using BIGSdb software. In C. jejuni this showed a nine-fold increase in resistance to fluoroquinolones from 1997 to 2018. Tetracycline resistance was also common, with higher initial resistance (1997) and less substantial change over time. Resistance to aminoglycosides or macrolides remained low in human cases across all time periods. Among C. jejuni food animal isolates, fluoroquinolone resistance was common among isolates from chicken and substantially less common among ruminants, ducks or pigs. Tetracycline resistance was common across chicken, duck and pig but lower among ruminant origin isolates. In C. coli resistance to all four antimicrobial classes rose from low levels in 1997. The fluoroquinolone rise appears to have levelled off earlier and among animals, levels are high in duck as well as chicken isolates, although based on small sample sizes, macrolide and aminoglycoside resistance, was substantially higher than for C. jejuni among humans and highest among pig origin isolates. Tetracycline resistance is high in isolates from pigs and the very small sample from ducks. Antibiotic use following diagnosis was relatively high (43.4%) among respondents in the human surveillance study. Moreover, it varied substantially across sites and was highest among non-elderly adults compared to older adults or children suggesting opportunities for improved antimicrobial stewardship. The study also found evidence for stable lineages over time across human and source animal species as well as some tighter genomic clusters that may represent outbreaks. The genomic dataset will allow extensive further work beyond the specific goals of the study. This has been made accessible on the web, with access supported by data visualisation tools.