82 research outputs found
Moduli stabilization with Fayet-Iliopoulos uplift
In the recent years, phenomenological models of moduli stabilization were
proposed, where the dynamics of the stabilization is essentially
supersymmetric, whereas an O'Rafearthaigh supersymmetry breaking sector is
responsible for the "uplift" of the cosmological constant to zero. We
investigate the case where the uplift is provided by a Fayet-Iliopoulos sector.
We find that in this case the modulus contribution to supersymmetry breaking is
larger than in the previous models. A first consequence of this class of
constructions is for gauginos, which are heavier compared to previous models.
In some of our explicit examples, due to a non-standard gauge-mediation type
negative contribution to scalars masses, the whole superpartner spectrum can be
efficiently compressed at low-energy. This provides an original phenomenology
testable at the LHC, in particular sleptons are generically heavier than the
squarks.Comment: 29 pages, 2 figure
SUSY flavor structure of generic 5D supergravity models
We perform a comprehensive and systematic analysis of the SUSY flavor
structure of generic 5D supergravity models on with multiple
-odd vector multiplets that generate multiple moduli. The SUSY flavor
problem can be avoided due to contact terms in the 4D effective K\"ahler
potential peculiar to the multi-moduli case. A detailed phenomenological
analysis is provided based on an illustrative model.Comment: 37 pages, 7 figures, Sec.4 is modifie
Genome-wide association study of eosinophilic granulomatosis with polyangiitis reveals genomic loci stratified by ANCA status
Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare inflammatory disease of unknown cause. 30% of patients have anti-neutrophil cytoplasmic antibodies (ANCA) specific for myeloperoxidase (MPO). Here, we describe a genome-wide association study in 676 EGPA cases and 6,809 controls, that identifies 4 EGPA-associated loci through conventional case-control analysis, and 4 additional associations through a conditional false discovery rate approach. Many variants are also associated with asthma and six are associated with eosinophil count in the general population. Through Mendelian randomisation, we show that a primary tendency to eosinophilia contributes to EGPA susceptibility. Stratification by ANCA reveals that EGPA comprises two genetically and clinically distinct syndromes. MPO+ ANCA EGPA is an eosinophilic autoimmune disease sharing certain clinical features and an HLA-DQ association with MPO+ ANCA-associated vasculitis, while ANCA-negative EGPA may instead have a mucosal/barrier dysfunction origin. Four candidate genes are targets of therapies in development, supporting their exploration in EGPA
Integrated analyses of single-cell atlases reveal age, gender, and smoking status associations with cell type-specific expression of mediators of SARS-CoV-2 viral entry and highlights inflammatory programs in putative target cells
The COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, creates an urgent need for identifying molecular mechanisms that mediate viral entry, propagation, and tissue pathology. Cell membrane bound angiotensin-converting enzyme 2 (ACE2) and associated proteases, transmembrane protease serine 2 (TMPRSS2) and Cathepsin L (CTSL), were previously identified as mediators of SARS-CoV2 cellular entry. Here, we assess the cell type-specific RNA expression of ACE2, TMPRSS2, and CTSL through an integrated analysis of 107 single-cell and single-nucleus RNA-Seq studies, including 22 lung and airways datasets (16 unpublished), and 85 datasets from other diverse organs. Joint expression of ACE2 and the accessory proteases identifies specific subsets of respiratory epithelial cells as putative targets of viral infection in the nasal passages, airways, and alveoli. Cells that co-express ACE2 and proteases are also identified in cells from other organs, some of which have been associated with COVID-19 transmission or pathology, including gut enterocytes, corneal epithelial cells, cardiomyocytes, heart pericytes, olfactory sustentacular cells, and renal epithelial cells. Performing the first meta-analyses of scRNA-seq studies, we analyzed 1,176,683 cells from 282 nasal, airway, and lung parenchyma samples from 164 donors spanning fetal, childhood, adult, and elderly age groups, associate increased levels of ACE2, TMPRSS2, and CTSL in specific cell types with increasing age, male gender, and smoking, all of which are epidemiologically linked to COVID-19 susceptibility and outcomes. Notably, there was a particularly low expression of ACE2 in the few young pediatric samples in the analysis. Further analysis reveals a gene expression program shared by ACE2(+)TMPRSS2(+) cells in nasal, lung and gut tissues, including genes that may mediate viral entry, subtend key immune functions, and mediate epithelial-macrophage cross-talk. Amongst these are IL6, its receptor and co-receptor, IL1R, TNF response pathways, and complement genes. Cell type specificity in the lung and airways and smoking effects were conserved in mice. Our analyses suggest that differences in the cell type-specific expression of mediators of SARS-CoV-2 viral entry may be responsible for aspects of COVID-19 epidemiology and clinical course, and point to putative molecular pathways involved in disease susceptibility and pathogenesis
Assessment of systemic AAV-microdystrophin gene therapy in the GRMD model of Duchenne muscular dystrophy
Duchenne muscular dystrophy (DMD) is a progressive muscle wasting disease caused by the absence of dystrophin, a membrane-stabilizing protein encoded by the DMD gene. Although mouse models of DMD provide insight into the potential of a corrective therapy, data from genetically homologous large animals, such as the dystrophin-deficient golden retriever muscular dystrophy (GRMD) model, may more readily translate to humans. To evaluate the clinical translatability of an adeno-associated virus serotype 9 vector (AAV9)–microdystrophin (μDys5) construct, we performed a blinded, placebo-controlled study in which 12 GRMD dogs were divided among four dose groups [control, 1 × 1013 vector genomes per kilogram (vg/kg), 1 × 1014 vg/kg, and 2 × 1014 vg/kg; n = 3 each], treated intravenously at 3 months of age with a canine codon-optimized microdystrophin construct, rAAV9-CK8e-c-μDys5, and followed for 90 days after dosing. All dogs received prednisone (1 milligram/kilogram) for a total of 5 weeks from day-7 through day 28. We observed dose-dependent increases in tissue vector genome copy numbers; μDys5 protein in multiple appendicular muscles, the diaphragm, and heart; limb and respiratory muscle functional improvement; and reduction of histopathologic lesions. As expected, given that a truncated dystrophin protein was generated, phenotypic test results and histopathologic lesions did not fully normalize. All administrations were well tolerated, and adverse events were not seen. These data suggest that systemically administered AAV-microdystrophin may be dosed safely and could provide therapeutic benefit for patients with DMD
Rapid escape of new SARS-CoV-2 Omicron variants from BA.2-directed antibody responses
In November 2021, Omicron BA.1, containing a raft of new spike mutations, emerged and quickly spread globally. Intense selection pressure to escape the antibody response produced by vaccines or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection then led to a rapid succession of Omicron sub-lineages with waves of BA.2 and then BA.4/5 infection. Recently, many variants have emerged such as BQ.1 and XBB, which carry up to 8 additional receptor-binding domain (RBD) amino acid substitutions compared with BA.2. We describe a panel of 25 potent monoclonal antibodies (mAbs) generated from vaccinees suffering BA.2 breakthrough infections. Epitope mapping shows potent mAb binding shifting to 3 clusters, 2 corresponding to early-pandemic binding hotspots. The RBD mutations in recent variants map close to these binding sites and knock out or severely knock down neutralization activity of all but 1 potent mAb. This recent mAb escape corresponds with large falls in neutralization titer of vaccine or BA.1, BA.2, or BA.4/5 immune serum
PROFIL WISATAWAN MUSEUM RADYA PUSTAKA SURAKARTA
Anggit Margaret, C9407031 2011. Profil Wisatawan Museum
Radya Pustaka Surakarta. Program Studi Diploma III Usaha Perjalanan
Wisata Fakultas Sastra Dan Seni Rupa Universitas Sebelas Maret Surakarta.
Penelitian tugas akhir ini mengkaji tentang Profil Wisatawan di
Museum Radya Pustaka Surakarta. Tujuan dari penelitian ini adalah untuk
mengetahui dari daerah mana saja wisatawan yang berkunjung ke Museum
Radya Pustaka, bagaimana ciri-ciri wisatawan yang berkunjung ke Museum
Radya Pustaka serta harapan-harapan yang diinginkan wisatawan terhadap
Museum Radya Pustaka.
Penelitian dilakukan dengan metode kualitatif. Pengumpulan data
dilakukan melalui wawancara dengan narasumber wisatawan yang berkujung
di Museum Radya Pustaka Surakarta tempat penulis melakukan penelitian,
serta studi pustaka dan studi dokumen guna menambah sumber data.
Hasil penelitian menunjukkan bahwa (1) Sebagian besar wisatawan
yang datang berasal dari Semarang sebesar 32%. (2) Mayoritas wisatawan
yang berkunjung ke Museum Radya Pustaka berusia antara 17-25 tahun dan
kebanyakan dari mereka adalah pelajar atau mahasiswa dengan prosentase
52%. (3) Sebagian besar wisatawan yang datang ke Museum Radya Pustaka
adalah bertujuan untuk melakukan penelitian yaitu sebesar 34%. (4) Harapan
wisatawan yang berkunjung terhadap kelangsungan Museum Radya Pustaka
sebagian besar adalah agar ditingkatkan lagi pengelolaan dan keamanan
museum, agar kejadian hilangnya benda-benda koleksi museum tidak terulang
lagi dikemudian hari.
Kesimpulan dari hasil penelitian ini bahwa wisatawan yang berkujung
ke Museum Radya Pustaka Surakarta mayoritas berasal dari Semarang,
mayoritas berusia 17-25 tahun dan kebanyakan dari mereka adalah berprofesi
sebagai pelajar dan mahasiswa. Kebanyakan wisatawan yang datang bertujuan
untuk melakukan penelitian, serta harapan wisatawan terhadap Museum
Radya Pustaka adalah supaya lebih ditingkatkan lagi pengelolaan dan
keamanan museum
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