The innate immune response to HSV-1: glycoprotein mediated activation of dendritic cells

Herpes Simplex Virus (HSV) – 1 also known as Human Herpes Virus (HHV) – 1 is a common infectious agent of humans which can cause a wide variety of clinical outcomes, ranging from mild mucocutaneous lesions to long term morbidity and possible mortality. Viral entry into cells requires the co-ordinated action of at least four HSV-1 envelope glycoproteins: gB, gD and the heterodimer gHgL. Dendritic cells (DC) are the most potent antigen presenting cells and are likely to encounter the virus early after entry into the host. HSV-1 readily infects DC leading to a series of both morphological and functional changes, and yet the pathway induced by HSV-1 that leads to DC maturation has not been elucidated. This thesis aims to understand the role of the viral entry glycoproteins in the activation of DC and the consequent initiation of an immune response. Defining this role has important implications not only in understanding immunopathogenesis, but also in the study of HSV-1 as an immunotherapeutic vector, and in the design of an efficient HSV-1 vaccine. Monocyte-derived DCs (MDDC) were found to recognise and respond to the complex of four essential viral glycoproteins, independent of other viral proteins or nucleic acids. MDDC recognition of these four glycoproteins leads to the upregulation of a maturation phenotype and the production of type I interferon (IFN) as well as the induction of a strongly polarised TH1, IFN-γ dominated allogeneic T cell response. In contrast, monocyte-derived Langerhans cells (MDLC), display only partial maturation phenotype and do not produce type I IFN. Plasmacytoid DC (pDC) induce a strong type I IFN response to a viral infection, but not to the viral surface glycoproteins. In the context of natural HSV-1 infection, these results suggest a model in which at the site of HSV-1 infection, different DC sub-populations respond differently to a viral infection and to glycoproteins expressed on the surface of infected cells in order to provide an effective immune response

Responding to Change: Girl Scouts, Race, and the Feminist Movement

The purpose of the Girl Scouts of the United States of America (GSUSA) is to teach girls to be giving, self-sufficient, and independent in their homes and communities through volunteer work and earning merit badges. Open to all girls since its inception, the GSUSA offers Girl Scouts training in both gender-conforming and nontraditional vocations. However, during the first half of the twentieth century, segregation and domesticity was emphasized in American society. The organization began to focus less on careers, independence, and racial inclusion to preparing predominately white girls to be good wives and mothers. As Black Power and women’s liberation gained momentum in the early 1970s, the GSUSA decided to increase its racial diversity and move in a more feminist direction by nominating Betty Friedan to the National Board of Directors and endorsing the Equal Rights Amendment. Despite the anti-feminist backlash from the membership, the GSUSA continued to support women’s liberation

In Defense of Lawyers

Conservative judge challenges Quayle statistics

Voltammetrische Detektierung der DNA-Hybridisierung von Oligonukleotiden und PCR-Produkten an Goldelektroden mit Osmiumtetroxid als kovalentem Marker

Ein neu erfundenes Verfahren zur Markierung von Oligonukleotiden mit dem elektrochemisch aktiven Komplex [OsO4(bipy)] unter Zuhilfenahme eines Schutzstranges wurde erstmals bei längerkettigen Nukleinsäuren und PCR(Polymerase-Kettenreaktion)-Produkten angewendet. Da dieses Verfahren nur an einzelsträngigen Nukleinsäureabschnitten durchgeführt werden kann, wurde nach verschiedenen Möglichkeiten gesucht, diese zu erzeugen. Die Detektierung der dann markierten Einzelstränge erfolgte voltammetrisch, nachdem eine Hybridisierung mit dem auf einer Goldelektrode immobilisierten Komplementärstrang erfolgte. Durch die Untersuchung verschiedener Einflüsse wie beispielsweise Temperatur, Reaktionsdauer und Konvektion konnten Markierungsreaktion und Hybridisierungsvorgang optimiert werden.A new invented method for labelling oligonucleotides with the electrochemical active complex [OsO4(bipy)] by means of a protection strand was adopted to long-chain nucleic acids and PCR(polymerase chain reaction)-products for the first time. Due to the fact, that this labelling reaction can only be performed at single-stranded nucleic acids, it was searched for different ways to create them. The detection of the labelled single-strands was carried out voltammetrically. Therefore the complementary probe strand, which was immobilized on a gold electrode had to hybridize with it. The investigation of different influences like temperature, reaction time and convection lead to an optimization of the labelling reaction and the hybridization event

A Fine-Grid Model for the ASRM Aft Segment with Gimballed Nozzle

Results from computational fluid dynamic analyses for complex three-dimensional internal flows in the Advanced Solid Rocket Motor (ASRM) are presented. In particular, flow visualization and tabulated results from a fine-grid model consisting of 1.5 M grid points for the ASRM Aft Segment at the l9-second burn time with an 8-degree nozzle gimbal angle are shown. The results from this model will enable characterization of various aspects of the ASRM internal environment, and in particular will allow an assessment of the heat transfer and stresses exerted on the submerged nozzle, casing insulation, and nozzle case joint

Expansion of antibody reactivity in the cerebrospinal fluid of multiple sclerosis patients – follow-up and clinical implications

BACKGROUND: An intrathecal polyspecific antibody response is a well known finding in multiple sclerosis. However, little is known about the evolution of intrathecal antibodies over time and their impact on the disease progress. Therefore, we focused in this study on the intrathecal polyspecific antibody response in multiple sclerosis. METHODS: Here we present a follow-up study of 70 patients with multiple sclerosis over 1 to 106 months. Serum and cerebrospinal fluid sample pairs were obtained from 1 to 5 consecutive lumbar punctures. CSF cell count, the IgG index, local IgG synthesis, oligoclonal bands and the antibody index for measles, rubella or varicella zoster were calculated. Results were analysed with regard to clinical characteristics of the patients. RESULTS: Once an intrathecal antibody response was established, it persisted. De novo antibody response against measles virus developed in 7% of the patients between the first and the second spinal tap. In two of seven patients where 5 consecutive CSF samples were available, the intrathecal antibody response expanded from one to three antigens. Furthermore, an intrathecal measles antibody production was associated with a rapid progression of the disease. CONCLUSION: These data stress the importance of activated B cells for the disease process and the clinical outcome in multiple sclerosis

RUMAH SUSUN BAGI ORANG ASING MENURUT PERATURAN PEMERINTAH RI. NOMOR. 18 TAHUN 2021

Tujuan dilakukannya penelitian ini yaitu untuk mengetahui bagaimana kebijakan pemerintah RI dalam menerbitkan suatu peraturan pemerintah tapi tidak bersumber pada udang-undang yang derajatnya lebih tinggi dan apakah layak orang asing mendapatkan hak milik dan mempunyai hak waris atas bidang tanah di Indonesia, yang mana dengan metode penelitian hukum normatif disimpulkan: 1. Rumah susun atau Satuan rumah susun dapat di miliki baik oleh warga Negara Indonesia maupun orang asing setelah memenuhi syarat dan layak untuk tinggal di rumah susun tersebut dan khusus buat orang asing kalau lokasi satuan rumah susun tersebut di bangun di lokasi kawasan ekonomi khusus, bandara terbuka, pelabuhan – pelabuhan terbuka atau lokasi yang telah di tentukan oleh pemerintah. Pemanfaatan tanah untuk di bangun satuan rumah susun harus sesuai renccana tata ruang wilayah yang pembangunannya harus menyesuaikan kesepadanan jalan umum serta fasilitas umum lainnya. 2. Menurut peraturan pemerintah RI nomor. 18 tahun 2021 tentang hak pengelolaan, hak atas tanah satuan rumah susun dan pendaftaran tanah orang asing yang tinggal atau berdomisili tetap di Indonesia berhak memperoleh hak milik atas bidang tanah di Indonesia bahkan apabila orang asing tersebut meninggal maka keluarganya atau anak – anaknya berhak mendapatkan hak waris atas bidang tanah tersbut. Sebelum berlakunya peraturan pemerintah RI nomor. 18 tahun 2021 tentang hak pengelolaan, hak atas tanah satuan rumah susun dan pendaftaran tanah pemanfaatan tanah di Indonesia oleh orang asing sifatnya terbatas yakni bagi orang perorang hanya 10 tahun sedangkan menyangkut kantor – kantor perwakilan atau kantor perwakilan Negara asing di berikan hak pakai selama di gunakan dan dalam undang – undang RI nomor. 5 tahun 1960 tentang peratusan dasar pokok – pokok Agraria pasal. 21 yang berhak mempunyai hak milik atas bidang tanah di Indonesia adalah warga Negara Indonesia saja tidak temasuk orang asing.Kata kunci: rumah susun; orang asing

Mouse invariant chain γ exhibits structural homology to both polymorphic subunits of the α,β-core complex of I-Ak antigens

AbstractThe 3 major constituents of the I-Ak subregion-associated complex α, β and γ were obtained from splenocytes in homogeneous form by differential isolation methods. α, β and γ were compared on the primary structural level by enzymatic fragmentation procedures and tryptic peptide map analysis of radiolabeled proteins. The data indicate that the invariant chain γ exhibits extensive structural homology to the polymorphic β-light and the α-heavy chain. Thus, although not being encoded within the MHC γ appears to belong structurally to the MHC-encoded class II proteins

Biosimilars and cancer treatment of older patients

AbstractBiosimilar monoclonal antibodies are being developed globally to meet clinical demand in oncology and potentially provide greater access to biologic therapies for patients with cancer, including older patients. In this supplement, we present an overview of the development, approval requirements, and characteristics of biosimilar monoclonal antibodies that may help practicing oncologists and other healthcare providers to acquire familiarity with this new group of therapeutic biologic agents. Furthermore, we review and discuss some of the challenges and potential strategies for the management of older patients with cancer, who represent an increasing population in many countries