The history of malarial fever and contributions to it Ronald Ross.

Thesis (M.A.)--Boston Universit

KONFLIK BATIN TOKOH UTAMA DALAM NOVEL DAN HUJAN PUN BERHENTI KARYA FARIDA SUSANTY : TINJAUAN PSIKOLOGI SASTRA

ABSTRAK Whiwy Devico Arafat. 1610722005. Judul Skripsi: Konflik Batin Tokoh Utama dalam Novel Dan Hujan Pun Berhenti karya Farida Susanty. Pembimbing I Dr. Fadlillah, M.Si, Pembimbing II Dr. Syafril, M.Si. Jurusan Sastra Indonesia Fakultas Ilmu Budaya. Universitas Andalas. Padang. 2021. Novel Dan Hujan Pun Berhenti menceritakan kisah para tokoh remaja yang dihadapkan dengan permasalahan yang cukup kompleks dalam hidupnya. Mereka mendapat Tekanan dari masa lalu, sehingga menimbulkan gejolak kejiwaan dalam dirinya. Pembahasan dalam sebuah penelitian ini yaitu menjelaskan konflik batin tokoh utama dalam novel Dan Hujan Pun Berhenti karya Farida Susanty ditinjau dari aspek Id, Ego dan Superego dan apa yang menyebabkan konflik batin tokoh utama dalam novel Dan Hujan Pun Berhenti karya Farida Susanty dengan menggunakan teori Sigmund Freud. Konflik batin yang ada dalam Novel Dan Hujan Pun Berhenti karya Farida Susanty yaitu keinginan yang tak terpenuhi, yakni keinginan memenuhi agar Id terpenuhi dengan kuatnya. Keinginan sangat kuat, sehingga menimbulkan stres. Akibat dari keinginan itu ia berusaha menghidupkan kembali sosok Iris (perempuan yang sudah meninggal) ke dalam diri Spiza. Artinya, tidak mampu lagi membedakan antara imajinasi dengan realita. Keinginan untuk bertemu, rasa sakit, sakit hati, rasa gelisah, rasa marah, tanggung jawab moral, keinginan untuk menyelamatkan, dan rasa bersalah. Sedangkan penyebab terjadinya konflik batin yaitu, Leo memiliki keluarga yang yang tidak harmonis, Leo memiliki tekanan batin karena merasa tidak diterima oleh orang di sekitarnya, dan Leo kehilangan orang yang dicintainya yaitu Iris dan Ibunya. Penelitian dengan cara mengumpulkan data dimulai dengan membaca novel Dan Hujan Pun Berhenti karya Farida Susanty dan mengumpulkan bahan- bahan yang memiliki kaitan langsung dengan penelitian ini berupa tulisan dan buku-buku, situs, maupun studi kepustakaan. Penganalisisan data menggunakan metode deskriptif analisis yaitu memberikan penjelasan tentang fakta-fakta yang ada. Kata Kunci : Konflik Batin, Id, Ego, Superego, Novel Dan Hujan Pun Berhent

Paring Down HIV Env: Design and Crystal Structure of a Stabilized Inner Domain of HIV-1 gp120 Displaying a Major ADCC Target of the A32 Region

SummaryEvidence supports a role of antibody-dependent cellular cytotoxicity (ADCC) toward transitional epitopes in the first and second constant (C1-C2) regions of gp120 (A32-like epitopes) in preventing HIV-1 infection and in vaccine-induced protection. Here, we describe the first successful attempt at isolating the inner domain (ID) of gp120 as an independent molecule that encapsulates the A32-like region within a minimal structural unit of the HIV-1 Env. Through structure-based design, we developed ID2, which consists of the ID expressed independently of the outer domain and stabilized in the CD4-bound conformation by an inter-layer disulfide bond. ID2 expresses C1-C2 epitopes in the context of CD4-triggered full-length gp120 but without any known neutralizing epitope present. Thus, ID2 represents a novel probe for the analysis and/or selective induction of antibody responses to the A32 epitope region. We also present the crystal structure of ID2 complexed with mAb A32, which defines its epitope

Spatial heterogeneity and peptide availability determine CTL killing efficiency in vivo

The rate at which a cytotoxic T lymphocyte (CTL) can survey for infected cells is a key ingredient of models of vertebrate immune responses to intracellular pathogens. Estimates have been obtained using in vivo cytotoxicity assays in which peptide-pulsed splenocytes are killed by CTL in the spleens of immunised mice. However the spleen is a heterogeneous environment and splenocytes comprise multiple cell types. Are some cell types intrinsically more susceptible to lysis than others? Quantitatively, what impacts are made by the spatial distribution of targets and effectors, and the level of peptide-MHC on the target cell surface? To address these questions we revisited the splenocyte killing assay, using CTL specific for an epitope of influenza virus. We found that at the cell population level T cell targets were killed more rapidly than B cells. Using modeling, quantitative imaging and in vitro killing assays we conclude that this difference in vivo likely reflects different migratory patterns of targets within the spleen and a heterogeneous distribution of CTL, with no detectable difference in the intrinsic susceptibilities of the two populations to lysis. Modeling of the stages involved in the detection and killing of peptide-pulsed targets in vitro revealed that peptide dose influenced the ability of CTL to form conjugates with targets but had no detectable effect on the probability that conjugation resulted in lysis, and that T cell targets took longer to lyse than B cells. We also infer that incomplete killing in vivo of cells pulsed with low doses of peptide may be due to a combination of heterogeneity in peptide uptake and the dissociation, but not internalisation, of peptide-MHC complexes. Our analyses demonstrate how population-averaged parameters in models of immune responses can be dissected to account for both spatial and cellular heterogeneity

Application of area scaling analysis to identify natural killer cell and monocyte involvement in the GranToxiLux antibody dependent cell-mediated cytotoxicity assay

Several different assay methodologies have been described for the evaluation of HIV or SIV-specific antibody-dependent cell-mediated cytotoxicity (ADCC). Commonly used assays measure ADCC by evaluating effector cell functions, or by detecting elimination of target cells. Signaling through Fc receptors, cellular activation, cytotoxic granule exocytosis, or accumulation of cytolytic and immune signaling factors have been used to evaluate ADCC at the level of the effector cells. Alternatively, assays that measure killing or loss of target cells provide a direct assessment of the specific killing activity of antibodies capable of ADCC. Thus, each of these two distinct types of assays provides information on only one of the critical components of an ADCC event; either the effector cells involved, or the resulting effect on the target cell. We have developed a simple modification of our previously described high-throughput ADCC GranToxiLux (GTL) assay that uses area scaling analysis (ASA) to facilitate simultaneous quantification of ADCC activity at the target cell level, and assessment of the contribution of natural killer cells and monocytes to the total observed ADCC activity when whole human peripheral blood mononuclear cells are used as a source of effector cells. The modified analysis method requires no additional reagents and can, therefore, be easily included in prospective studies. Moreover, ASA can also often be applied to pre-existing ADCC-GTL datasets. Thus, incorporation of ASA to the ADCC-GTL assay provides an ancillary assessment of the ability of natural and vaccine-induced antibodies to recruit natural killer cells as well as monocytes against HIV or SIV; or to any other field of research for which this assay is applied

Lack of Protection following Passive Transfer of Polyclonal Highly Functional Low-Dose Non-Neutralizing Antibodies

Recent immune correlates analysis from the RV144 vaccine trial has renewed interest in the role of non-neutralizing antibodies in mediating protection from infection. While neutralizing antibodies have proven difficult to induce through vaccination, extra-neutralizing antibodies, such as those that mediate antibody-dependent cellular cytotoxicity (ADCC), are associated with long-term control of infection. However, while several non-neutralizing monoclonal antibodies have been tested for their protective efficacy in vivo, no studies to date have tested the protective activity of naturally produced polyclonal antibodies from individuals harboring potent ADCC activity. Because ADCC-inducing antibodies are highly enriched in elite controllers (EC), we passively transferred highly functional non-neutralizing polyclonal antibodies, purified from an EC, to assess the potential impact of polyclonal non-neutralizing antibodies on a stringent SHIV-SF162P3 challenge in rhesus monkeys. Passive transfer of a low-dose of ADCC inducing antibodies did not protect from infection following SHIV-SF162P3 challenge. Passively administered antibody titers and gp120-specific, but not gp41-specific, ADCC and antibody induced phagocytosis (ADCP) were detected in the majority of the monkeys, but did not correlate with post infection viral control. Thus these data raise the possibility that gp120-specific ADCC activity alone may not be sufficient to control viremia post infection but that other specificities or Fc-effector profiles, alone or in combination, may have an impact on viral control and should be tested in future passive transfer experiments