236 research outputs found

    Pengakuan Masyarakat Adat Tentang Hak Ulayat

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    Penelitian ini dilakukan bertujuan untuk mengetahui bagaimana eksistensi masyarakat adat dan hukum adat di Indonesiadan bagaimana pengakuan hak ulayat masyarakat adat dalam hukum pertanahan serta bagaimana keberadaan hak ulayat masyarakat adat sebagai hak asasi manusia dalam konstitusi di indonesi. Penelitian ini menggunakan metode penelitian yuridis normatif dan dapat disimpulkan, bahwa: 1. Eksistensi masyarakat adat dan hukum adat di Indonesia setidak-tidaknya dapat dilihat dari dua hukum adat sampai saat ini masih relevan untuk dipertahankan sebagai hukum yang berlaku di Indonesia. Bentuk sosiologis masyarakat hukum adat yang majemuk menjadikan hukum yang berlaku tentu saja bersifat majemuk pula, dan hukum yang majemuk tersebut menunjukkan kepribadian asli bangsa Indonesia yang multikultur. Di samping itu argument yuridis, di mana pengakuan terhadap keberlakuan hukum adat secara normatif telah diatur sejak dari masa Hindia Belanda dalam Pasal 131 ayat (2) sub b Indische Staatsregering yang menyatakan, bagi golongan bumi putera (pribumi) berlaku hukum adatnya. Kemudian pengakuan secara yuridis terhadap keberlakuan masyarakat hukum adat dalam Amandemen Kedua UUD 1945 menjadikan keberadaan hukum adat di Indonesia semakin kukuh, karena telah dianggap sebagai hak konstitusional warga negara yang dimiliki oleh masyarakat hukum adat. 2. Dalam UUPA dinyatakan bahwa hukum tanah didasarkan pada hukum adat. Dapat diartikan bahwa segala sesuatu mengenai pertanahan harus digali dari hukum adat. 3. Dinamika konstitusional Indonesia memperlihatkan pasang surut diskursus tentang hak ulayat. Tetapi dalam tataran gerakan, perjuangan hak-hak masyarakat adat semakin menguat baik secara nasional maupun Internasional

    Endoplasmic reticulum aminopeptidase 1 (ERAP1) polymorphism relevant to inflammatory disease shapes the peptidome of the birdshot chorioretinopathy-associated HLA-A∗29:02 Antigen

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    Birdshot chorioretinopathy is a rare ocular inflammation whose genetic association with HLA-A∗29:02 is the highest between a disease and a major histocompatibility complex (MHC) molecule. It belongs to a group of MHCI- Associated inflammatory disorders, also including ankylosing spondylitis, psoriasis, and Behç et's disease, for which endoplasmic reticulum aminopeptidases (ERAP) 1 and/or 2 have been identified as genetic risk factors. Since both enzymes are involved in the processing of MHC-I ligands, it seems reasonable that common peptide- mediated mechanisms may underlie the pathogenesis of these diseases. In this study, comparative immunopeptidomics was used to characterize >5000 A∗29:02 ligands and quantify the effects of ERAP1 polymorphism and expression on the A∗29:02 peptidome in human cells. The peptides predominant in an active ERAP1 context showed a higher frequency of nonamers and bulkier amino acid side chains at multiple positions, compared with the peptides predominant in a less active ERAP1 background. Thus, ERAP1 polymorphism has a large influence, shaping the A∗29:02 peptidome through length-dependent and length-independent effects. These changes resulted in increased affinity and hydrophobicity of A∗29:02 ligands in an active ERAP1 context. The results reveal the nature of the functional interaction between A∗29:02 and ERAP1 and suggest that this enzyme may affect the susceptibility to birdshot chorioretinopathy by altering the A∗29:02 peptidome. The complexity of these alterations is such that not only peptide presentation but also other potentially pathogenic features could be affectedThis work was supported by grants SAF2011/25681 (Plan Nacional de I+D+i) to JALC, Binational Science Foundation Grant 2009393 to AA, and an institutional grant of the Fundacion Ramon Areces to the CBMS

    Heat and mass transfer on MHD squeezing flow of jeffrey nanofluid in horizontal channel through permeable medium

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    The heat and mass transfer on time dependent hydrodynamic squeeze flow of Jeffrey nanofluid across two plates over permeable medium in the slip condition with heat generation/absorption, thermal radiation and chemical reaction are investigated. The impacts of Brownian motion and thermophoresis is examined in the Buongiorno's nanofluid model. Conversion of the governing partial differential equations to the ordinary differential equations is conducted via similarity transformation. The dimensionless equations are solved by imposing numerical method of Keller-box. The outputs are compared with previous reported works in the journals for the validation of the present outputs and found in proper agreement. The behavior of velocity, temperature, and nanoparticles concentration profiles by varying the pertinent parameters are examined. Findings portray that the acceleration of the velocity profile and the wall shear stress is due to the squeezing of plates. Furthermore, the velocity, temperature and concentration profile decline with boost in Hartmann number and ratio of relaxation to retardation times. It is discovered that the rate of heat transfer and temperature profile increase when viscous dissipation, thermophoresis and heat source/sink rises. In contrast, the increment of thermal radiation reduces the temperature and enhances the heat transfer rate. Besides, the mass transfer rate decelerates for increasing Brownian motion in nanofluid, while it elevates when chemical reaction and thermophoresis increases

    Slip effects on mhd squeezing flow of jeffrey nanofluid in horizontal channel with chemical reaction

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    The heat and mass transfer characteristics on hydromagnetic squeeze flow of Jeffrey nanofluid between two plates over a permeable medium by slip condition with the influences of viscous dissipation and chemical reaction is examined. Buongiorno’s nanofluid model, which includes Brownian motion and thermophoresis impacts, is implemented in this research. The gov-erning nonlinear partial differential equations are transformed to the nonlinear ordinary differential equations via asimilarity transformation. The transformed equations are solved by employing numerical techniques of Keller-box. A comparison of the skin friction coefficient, Nusselt and Sherwood numbers with reported outputs in the journals are carried out to validate the present outputs. An excellent agreement is found. The results show that the squeezing of plates accelerates the velocity and wall shear stress. Furthermore, the velocity, temperature and concentration profile decrease when the Hartmann number and ratio of relaxation and retardation times increases. The raise in thermophoresis and viscous dissipation elevate the temperature profile and the heat transfer rate. Furthermore, the mass transfer rate declines due to the strong Brownian motion in the nanofluid, whereas it increases with the addition of chemical reaction and thermophoresis

    Numerous proteins with unique characteristics are degraded by the 26S proteasome following monoubiquitination

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    The "canonical" proteasomal degradation signal is a substrate-anchored polyubiquitin chain. However, a handful of proteins were shown to be targeted following monoubiquitination. In this study, we established-in both human and yeast cells-a systematic approach for the identification of monoubiquitination-dependent proteasomal substrates. The cellular wild-type polymerizable ubiquitin was replaced with ubiquitin that cannot form chains. Using proteomic analysis, we screened for substrates that are nevertheless degraded under these conditions compared with those that are stabilized, and therefore require polyubiquitination for their degradation. For randomly sampled representative substrates, we confirmed that their cellular stability is in agreement with our screening prediction. Importantly, the two groups display unique features: monoubiquitinated substrates are smaller than the polyubiquitinated ones, are enriched in specific pathways, and, in humans, are structurally less disordered. We suggest that monoubiquitination-dependent degradation is more widespread than assumed previously, and plays key roles in various cellular processes

    Assessment of Symptom, Disability, and Financial Trajectories in Patients Hospitalized for COVID-19 at 6 Months

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    IMPORTANCE: Individuals who survived COVID-19 often report persistent symptoms, disabilities, and financial consequences. However, national longitudinal estimates of symptom burden remain limited. OBJECTIVE: To measure the incidence and changes over time in symptoms, disability, and financial status after COVID-19-related hospitalization. DESIGN, SETTING, AND PARTICIPANTS: A national US multicenter prospective cohort study with 1-, 3-, and 6-month postdischarge visits was conducted at 44 sites participating in the National Heart, Lung, and Blood Institute Prevention and Early Treatment of Acute Lung Injury Network\u27s Biology and Longitudinal Epidemiology: COVID-19 Observational (BLUE CORAL) study. Participants included hospitalized English- or Spanish-speaking adults without severe prehospitalization disabilities or cognitive impairment. Participants were enrolled between August 24, 2020, and July 20, 2021, with follow-up occurring through March 30, 2022. EXPOSURE: Hospitalization for COVID-19 as identified with a positive SARS-CoV-2 molecular test. MAIN OUTCOMES AND MEASURES: New or worsened cardiopulmonary symptoms, financial problems, functional impairments, perceived return to baseline health, and quality of life. Logistic regression was used to identify factors associated with new cardiopulmonary symptoms or financial problems at 6 months. RESULTS: A total of 825 adults (444 [54.0%] were male, and 379 [46.0%] were female) met eligibility criteria and completed at least 1 follow-up survey. Median age was 56 (IQR, 43-66) years; 253 (30.7%) participants were Hispanic, 145 (17.6%) were non-Hispanic Black, and 360 (43.6%) were non-Hispanic White. Symptoms, disabilities, and financial problems remained highly prevalent among hospitalization survivors at month 6. Rates increased between months 1 and 6 for cardiopulmonary symptoms (from 67.3% to 75.4%; P = .001) and fatigue (from 40.7% to 50.8%; P \u3c .001). Decreases were noted over the same interval for prevalent financial problems (from 66.1% to 56.4%; P \u3c .001) and functional limitations (from 55.3% to 47.3%; P = .004). Participants not reporting problems at month 1 often reported new symptoms (60.0%), financial problems (23.7%), disabilities (23.8%), or fatigue (41.4%) at month 6. CONCLUSIONS AND RELEVANCE: The findings of this cohort study of people discharged after COVID-19 hospitalization suggest that recovery in symptoms, functional status, and fatigue was limited at 6 months, and some participants reported new problems 6 months after hospital discharge

    UVB-Induced Tumor Heterogeneity Diminishes Immune Response in Melanoma

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    Although clonal neo-antigen burden is associated with improved response to immune therapy, the functional basis for this remains unclear. Here we study this question in a novel controlled mouse melanoma model that enables us to explore the effects of intra-tumor heterogeneity (ITH) on tumor aggressiveness and immunity independent of tumor mutational burden. Induction of UVB-derived mutations yields highly aggressive tumors with decreased anti-tumor activity. However, single-cell-derived tumors with reduced ITH are swiftly rejected. Their rejection is accompanied by increased T cell reactivity and a less suppressive microenvironment. Using phylogenetic analyses and mixing experiments of single-cell clones, we dissect two characteristics of ITH: the number of clones forming the tumor and their clonal diversity. Our analysis of melanoma patient tumor data recapitulates our results in terms of overall survival and response to immune checkpoint therapy. These findings highlight the importance of clonal mutations in robust immune surveillance and the need to quantify patient ITH to determine the response to checkpoint blockade

    Healthy cells functionally present TAP-independent SSR1 peptides: implications for selection of clinically relevant antigens

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    Tumors with an impaired transporter associated with antigen processing (TAP) present several endoplasmic reticulum-derived self-antigens on HLA class I (HLA-I) which are absent on healthy cells. Selection of such TAP-independent antigens for T cell-based immunotherapy should include analysis of their expression on healthy cells to prevent therapy-induced adverse toxicities. However, it is unknown how the absence of clinically relevant antigens on healthy cells needs to be validated. Here, we monitored TAP-independent antigen presentation on various healthy cells after establishing a T cell tool recognizing a TAP-independent signal sequence receptor 1-derived antigen. We found that most but not all healthy cells present this antigen under normal and inflammatory conditions, indicating that TAP-independent antigen presentation is a variable phenomenon. Our data emphasize the necessity of extensive testing of a wide variety of healthy cell types to define clinically relevant TAP-independent antigens that can be safely targeted by immunotherapy.Immunobiology of allogeneic stem cell transplantation and immunotherapy of hematological disease
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