Who is Like God? The Deer Hunter as Angelic Allegory

Michael Cimino’s The Deer Hunter utilizes Christian contexts and biblical motifs in order to present an allegory in which Michael (Robert De Niro) represents an angelic being. While Michael displays powers that parallel those of biblical angels, his lack of religious reverence and divine self-perception lead to a metaphorical fall in Vietnam. Michael’s friend Nick (Christopher Walken) is also an allegorical symbol for imperiled humanity in need of salvation. When Michael is unable to rescue Nick from a Russian roulette table in Saigon, Cimino’s film emerges as a theological statement about the problem of human violence and the necessity for hope in God

Ökologischer Anbau von Zierpflanzen und Baumschulerzeugnissen - Struktur, Entwicklung, Probleme, politischer Handlungsbedarf

In the Federal Organic Farming Scheme Project "Organic production of ornamental plants and nursery trees - structure of the industry, development, problems and required policy initiatives“a quantitative and qualitative survey of certified organic and conventional / integrated nurseries was carried out. The aim was to assess the current status of production and marketing of organic ornamentals in Germany and to provide an overview of the general framework of this industry. • Currently approximately 1 % of the nurseries producing ornamentals in Germany are organic. Considering the small scale of many of the organic units, the share of total sales (2.4 billion Euro or 7.6 % of agricultural production in 2001) is likely to be lower. • Field and greenhouse production of organic annuals and perennials constitutes an estimated 56 ha and 12 ha, respectively. Organic field and container production of trees and shrubs constitutes an estimated 370 ha and 7 ha, respectively. • 90% of the organic nurseries surveyed would choose organic production again, if faced with the question of conversion a second time. • Fewer problems than anticipated were encountered in production - even in pest and disease management. However, problems persist in weed control and continuity of nutrient supply from the growing media. Other challenges were the sourcing of organically acceptable inputs (such as seedlings or growing media) in the production of annuals and perennials. In tree nurseries especially the decline in plant vigour caused by the common practice of successive planting of rosaceae raised difficulties. • Marketing was quoted to be the biggest problem for nurseries which engage in direct marketing. Wholesalers anticipated the biggest problems with the continuity and consistency of the supply of quality product. • The majority of organic operations surveyed encountered financial difficulties during the conversion period and afterwards. • 32 % of growers from integrated operations have already considered organic production, but have - for economic reasons - not pursued this idea further. • The operations surveyed noted that organic standards need expansion and revisions to cover their industry; and that organic inspectors were lacking sufficient technical knowledge. State subsidies for organic ornamental nurseries were found to be inconsistent between the member states of the Federal Republic of Germany. • A high need for an organic advisory service for these types of operations was indicated, but has not been sufficiently met to date. Further, there was almost no research about the organic production of ornamentals. Conclusion Organic production of ornamentals, trees and shrubs is technically feasible - but for further development this sector requires improvement of the basic conditions such as market structure, advisory services, subsidies and research activities

Highly Efficient and Selective CAR-Gene Transfer Using CD4- and CD8-Targeted Lentiviral Vectors

Chimeric antigen receptor (CAR)-modified T cells have revealed promising results in the treatment of cancer, but they still need to overcome various hurdles, including a complicated manufacturing process. Receptor-targeted lentiviral vectors (LVs) delivering genes selectively to T cell subtypes may facilitate and improve CAR T cell generation, but so far they have resulted in lower gene delivery rates than conventional LVs (vesicular stomatitis virus VSV-LV). To overcome this limitation, we studied the effect of the transduction enhancer Vectofusin-1 on gene delivery to human T cells with CD4- and CD8-targeted LVs, respectively, encoding a second-generation CD19-CAR in conjunction with a truncated version of the low-affinity nerve growth factor receptor (�LNGFR) as reporter. Vectofusin-1 significantly enhanced the gene delivery of CD4- and CD8-LVs without a loss in target cell selectivity and killing capability of the generated CAR T cells. Notably, delivery rates mediated by VSV-LV were substantially reduced by Vectofusin-1. Interestingly, a transient off-target signal in samples treated with Vectofusin-1 was observed early after transduction. However, this effect was not caused by uptake and expression of the transgene in off-target cells, but rather it resulted from cell-bound LV particles having �LNGFR incorporated into their surface. The data demonstrate that gene transfer rates in the range of those mediated by VSV-LVs can be achieved with receptor-targeted LVs. © 2019 The Author(s

CD62L as target receptor for specific gene delivery into less differentiated human T lymphocytes

Chimeric antigen receptor (CAR)-expressing T cells are a complex and heterogeneous gene therapy product with variable phenotype compositions. A higher proportion of less differentiated CAR T cells is usually associated with improved antitumoral function and persistence. We describe in this study a novel receptor-targeted lentiviral vector (LV) named 62L-LV that preferentially transduces less differentiated T cells marked by the L-selectin receptor CD62L, with transduction rates of up to 70% of CD4+ and 50% of CD8+ primary T cells. Remarkably, higher amounts of less differentiated T cells are transduced and preserved upon long-term cultivation using 62L-LV compared to VSV-LV. Interestingly, shed CD62L neither altered the binding of 62L-LV particles to T cells nor impacted their transduction. The incubation of 2 days of activated T lymphocytes with 62L-LV or VSV-LV for only 24 hours was sufficient to generate CAR T cells that controlled tumor growth in a leukemia tumor mouse model. The data proved that potent CAR T cells can be generated by short-term ex vivo exposure of primary cells to LVs. As a first vector type that preferentially transduces less differentiated T lymphocytes, 62L-LV has the potential to circumvent cumbersome selections of T cell subtypes and offers substantial shortening of the CAR T cell manufacturing process

Expression of survivin detected by immunohistochemistry in the cytoplasm and in the nucleus is associated with prognosis of leiomyosarcoma and synovial sarcoma patients

<p>Abstract</p> <p>Background</p> <p>Survivin, a member of the inhibitor of apoptosis-protein family suppresses apoptosis and regulates cell division. It is strongly overexpressed in the vast majority of cancers. We were interested if survivin detected by immunohistochemistry has prognostic relevance especially for patients of the two soft tissue sarcoma entities leiomyosarcoma and synovial sarcoma.</p> <p>Methods</p> <p>Tumors of leiomyosarcoma (n = 24) and synovial sarcoma patients (n = 26) were investigated for their expression of survivin by immunohistochemistry. Survivin expression was assessed in the cytoplasm and the nucleus of tumor cells using an immunoreactive scoring system (IRS).</p> <p>Results</p> <p>We detected a survivin expression (IRS > 2) in the cytoplasm of 20 leiomyosarcomas and 22 synovial sarcomas and in the nucleus of 12 leiomyosarcomas and 9 synovial sarcomas, respectively. There was no significant difference between leiomyosarcoma and synovial sarcoma samples in their cytoplasmic or nuclear expression of survivin. Next, all sarcoma patients were separated in four groups according to their survivin expression in the cytoplasm and in the nucleus: group 1: negative (IRS 0 to 2); group 2: weak (IRS 3 to 4); group 3: moderate (IRS 6 to 8); group 4: strong (IRS 9 to 12). In a multivariate Cox's regression hazard analysis survivin expression detected in the cytoplasm or in the nucleus was significantly associated with overall survival of patients in group 3 (RR = 5.7; P = 0.004 and RR = 5.7; P = 0.022, respectively) compared to group 2 (reference). Patients whose tumors showed both a moderate/strong expression of survivin in the cytoplasm and a moderate expression of survivin in the nucleus (in both compartments IRS ≥ 6) possessed a 24.8-fold increased risk of tumor-related death (P = 0.003) compared to patients with a weak expression of survivin both in the cytoplasm and in the nucleus.</p> <p>Conclusion</p> <p>Survivin protein expression in the cytoplasma and in the nucleus detected by immunohistochemistry is significantly associated with prognosis of leiomyosarcoma and synovial sarcoma patients.</p

Active Zone Protein Bassoon Co-Localizes with Presynaptic Calcium Channel, Modifies Channel Function, and Recovers from Aging Related Loss by Exercise

The P/Q-type voltage-dependent calcium channels (VDCCs) are essential for synaptic transmission at adult mammalian neuromuscular junctions (NMJs); however, the subsynaptic location of VDCCs relative to active zones in rodent NMJs, and the functional modification of VDCCs by the interaction with active zone protein Bassoon remain unknown. Here, we show that P/Q-type VDCCs distribute in a punctate pattern within the NMJ presynaptic terminals and align in three dimensions with Bassoon. This distribution pattern of P/Q-type VDCCs and Bassoon in NMJs is consistent with our previous study demonstrating the binding of VDCCs and Bassoon. In addition, we now show that the interaction between P/Q-type VDCCs and Bassoon significantly suppressed the inactivation property of P/Q-type VDCCs, suggesting that the Ca2+ influx may be augmented by Bassoon for efficient synaptic transmission at NMJs. However, presynaptic Bassoon level was significantly attenuated in aged rat NMJs, which suggests an attenuation of VDCC function due to a lack of this interaction between VDCC and Bassoon. Importantly, the decreased Bassoon level in aged NMJs was ameliorated by isometric strength training of muscles for two months. The training increased Bassoon immunoreactivity in NMJs without affecting synapse size. These results demonstrated that the P/Q-type VDCCs preferentially accumulate at NMJ active zones and play essential role in synaptic transmission in conjunction with the active zone protein Bassoon. This molecular mechanism becomes impaired by aging, which suggests altered synaptic function in aged NMJs. However, Bassoon level in aged NMJs can be improved by muscle exercise