Human Vault Nanoparticle Targeted Delivery of Antiretroviral Drugs to Inhibit Human Immunodeficiency Virus Type 1 Infection.

"Vaults" are ubiquitously expressed endogenous ribonucleoprotein nanoparticles with potential utility for targeted drug delivery. Here, we show that recombinant human vault nanoparticles are readily engulfed by certain key human peripheral blood mononuclear cells (PBMC), predominately dendritic cells, monocytes/macrophages, and activated T cells. As these cell types are the primary targets for human immunodeficiency virus type 1 (HIV-1) infection, we examined the utility of recombinant human vaults for targeted delivery of antiretroviral drugs. We chemically modified three different antiretroviral drugs, zidovudine, tenofovir, and elvitegravir, for direct conjugation to vaults. Tested in infection assays, drug-conjugated vaults inhibited HIV-1 infection of PBMC with equivalent activity to free drugs, indicating vault delivery and drug release in the cytoplasm of HIV-1-susceptible cells. The ability to deliver functional drugs via vault nanoparticle conjugates suggests their potential utility for targeted drug delivery against HIV-1

On Composite Two Higgs Doublet Models

We investigate composite two Higgs doublet models realized as pseudo Goldstone modes, generated through the spontaneous breaking of a global symmetry due to strong dynamic at the TeV scale. A detailed comparative survey of two possible symmetry breaking patterns, SU(5) -> SU(4) x U(1) and SU(5) x SU(4), is made. We point out choices for the Standard Model fermion representations that can alleviate some phenomenological constraints, with emphasis towards a simultaneous solution of anomalous Zb\bar{b} coupling and Higgs mediated Flavor Changing Neutral Currents. We also write down the kinetic lagrangian for several models leading to Two Higgs Doublets and identify the anomalous contributions to the T parameter. Moreover, we describe a model based on the breaking $SO(9)/SO(8)$ in which there is no tree-level breaking of custodial symmetry, discussing also the possible embeddings for the fermion fields.Comment: 17 pages. Mistake corrected, added one section on a T- and flavor safe model based on SO(9)/SO(8). Matches published versio

Generalized methods and solvers for noise removal from piecewise constant signals. II. New methods

Removing noise from signals which are piecewise constant (PWC) is a challenging signal processing problem that arises in many practical scientific and engineering contexts. In the first paper (part I) of this series of two, we presented background theory building on results from the image processing community to show that the majority of these algorithms, and more proposed in the wider literature, are each associated with a special case of a generalized functional, that, when minimized, solves the PWC denoising problem. It shows how the minimizer can be obtained by a range of computational solver algorithms. In this second paper (part II), using this understanding developed in part I, we introduce several novel PWC denoising methods, which, for example, combine the global behaviour of mean shift clustering with the local smoothing of total variation diffusion, and show example solver algorithms for these new methods. Comparisons between these methods are performed on synthetic and real signals, revealing that our new methods have a useful role to play. Finally, overlaps between the generalized methods of these two papers and others such as wavelet shrinkage, hidden Markov models, and piecewise smooth filtering are touched on

Collective Quartics from Simple Groups

This article classifies Little Higgs models that have collective quartic couplings. There are two classes of collective quartics: Special Cosets and Special Quartics. After taking into account dangerous singlets, the smallest Special Coset models are SU(5)/SO(5) and SU(6)/Sp(6). The smallest Special Quartic model is SU(5)/SU(3) x SU(2) x U(1) and has not previously been considered as a candidate Little Higgs model.Comment: 22 pages, 2 figure

Generalized methods and solvers for noise removal from piecewise constant signals. I. Background theory

Removing noise from piecewise constant (PWC) signals is a challenging signal processing problem arising in many practical contexts. For example, in exploration geosciences, noisy drill hole records need to be separated into stratigraphic zones, and in biophysics, jumps between molecular dwell states have to be extracted from noisy fluorescence microscopy signals. Many PWC denoising methods exist, including total variation regularization, mean shift clustering, stepwise jump placement, running medians, convex clustering shrinkage and bilateral filtering; conventional linear signal processing methods are fundamentally unsuited. This paper (part I, the first of two) shows that most of these methods are associated with a special case of a generalized functional, minimized to achieve PWC denoising. The minimizer can be obtained by diverse solver algorithms, including stepwise jump placement, convex programming, finite differences, iterated running medians, least angle regression, regularization path following and coordinate descent. In the second paper, part II, we introduce novel PWC denoising methods, and comparisons between these methods performed on synthetic and real signals, showing that the new understanding of the problem gained in part I leads to new methods that have a useful role to play

Detecting Horizontally Transferred and Essential Genes Based on Dinucleotide Relative Abundance

Various methods have been developed to detect horizontal gene transfer in bacteria, based on anomalous nucleotide composition, assuming that compositional features undergo amelioration in the host genome. Evolutionary theory predicts the inevitability of false positives when essential sequences are strongly conserved. Foreign genes could become more detectable on the basis of their higher order compositions if such features ameliorate more rapidly and uniformly than lower order features. This possibility is tested by comparing the heterogeneities of bacterial genomes with respect to strand-independent first- and second-order features, (i) G + C content and (ii) dinucleotide relative abundance, in 1 kb segments. Although statistical analysis confirms that (ii) is less inhomogeneous than (i) in all 12 species examined, extreme anomalies with respect to (ii) in the Escherichia coli K12 genome are typically co-located with essential genes

Heavy-light decay topologies as a new strategy to discover a heavy gluon

We study the collider phenomenology of the lightest Kaluza-Klein excitation of the gluon, G*, in theories with a warped extra dimension. We do so by means of a two-site effective lagrangian which includes only the lowest-lying spin-1 and spin-1/2 resonances. We point out the importance of the decays of G* to one SM plus one heavy fermion, that were overlooked in the previous literature. It turns out that, when kinematically allowed, such heavy-light decays are powerful channels for discovering the G*. In particular, we present a parton-level Montecarlo analysis of the final state Wtb that follows from the decay of G* to one SM top or bottom quark plus its heavy partner. We find that at \sqrt{s} = 7 TeV and with 10 fb^{-1} of integrated luminosity, the LHC can discover a KK gluon with mass in the range M_{G*} = (1.8 - 2.2) TeV if its coupling to a pair of light quarks is g_{G*qqbar} = (0.2-0.5) g_3. The same process is also competitive for the discovery of the top and bottom partners as well. We find, for example, that the LHC at \sqrt{s} = 7 TeV can discover a 1 TeV KK bottom quark with an integrated luminosity of (5.3 - 0.61) fb^{-1} for g_{G*qqbar} = (0.2-0.5) g_3.Comment: 36 pages, 13 figures. v2: a few typos corrected, comments added, version published in JHE

MEMPERKENALKAN LITERASI EKONOMI BERBASIS KULTURAL DI SD DAN SMP HKBP SIDORAME MEDAN

Program Pengabdian Kepada Masyarakat ini bertujuan untuk memberikan pelatihan peningkatan literasi bagi anak-anak Sekolah Dasar (SD) dan Sekolah Menengah Pertama (SMP) yang berfokus memberikan pendampingan informasi kepada para siswa maupun tenaga pengajar tentang pentingnya literasi ekonomi dalam pengembangan ilmu pengetahuan di masyarakat indonesia. Kegiatan ini dilaksanakan oleh dosen dan mahasiswa dari jurusan Pendidikan Ekonomi Fakultas Keguruan dan Ilmu Pendidikan, Universitas HKBP Nommensen Medan bersama dengan mahasiswa dari Universitas Czech. Pelaksanaan kegiatan Pengabdian Kepada Masyarakat dalam peningkatan literasi dimulai pada tanggal 25 juli 2022 dan selesai pada tanggal 26 juli 2022. Sebelumnya, telah dilakukan sosialisasi kepada SD 1 dan SMP Swasta HKBP Sidorame Medan mengenai kegiatan PKM Peningkatan Literasi. Berdasarkan kegiatan sosialisasi sebelumnya dapat di simpulkan bahwa penyebab rendahnya kemampuan literasi siswa adalah karena tradisi lisan yang masih mendarahdaging di masyarakat. Lebih jauh lagi, sistem pendidikan sekolah masih belum memberikan peluang tradisi literasi kepada siswa. Hal ini juga terjadi kepada siswa/siswi SD dan SMP HKBP Sidorame Medan. Masalah ini kemudian diminimalisir dengan melaksanakan kegiatan Program Pengabdian Masyarakat terkait literasi bagi siswa/siswi SD dan SMP. Program ini merupakan salah satu bidang penting dalam pengembangan literasi di sekolah. Hal positif yang akan diperoleh adalah bahwa ada sejumlah besar kelompok sasaran yang ter identifikasi, tidak hanya peserta didik tetapi juga pendidik. Guru sendiri harus mengekspos siswa untuk melek huruf serta literasi haruslah menjadi sebuah budaya

Low-scale warped extra dimension and its predilection for multiple top quarks

Within warped extra dimension models that explain flavor through geometry, flavor changing neutral current constraints generally force the Kaluza-Klein scale to be above many TeV. This creates tension with a natural electroweak scale. On the other hand, a much lower scale compatible with precision electroweak and flavor changing neutral current constraints is allowed if we decouple the Kaluza-Klein states of Standard Model gauge bosons from light fermions $c_{\rm light}\simeq c_b\simeq 0.5$ bulk mass parameters). The main signature for this approach is four top quark production via the Kaluza-Klein excitations' strong coupling to top quarks. We study single lepton, like-sign dilepton, and trilepton observables of four-top events at the Large Hadron Collider. The like-sign dilepton signature typically has the largest discovery potential for a strongly coupled right-handed top case (M_{KK} \sim 2-2.5 \TeV), while single lepton is the better when the left-handed top couples most strongly (M_{KK} \sim 2 \TeV). We also describe challenging lepton-jet collimation issues in the like-sign dilepton and trilepton channels. An alternative single lepton observable is considered which takes advantage of the many bottom quarks in the final state. Although searches of other particles may compete, we find that four top production via Kaluza-Klein gluons is most promising in a large region of this parameter space.Comment: 35 pages, 8 figures. discussions improved, references adde

Partially Supersymmetric Composite Higgs Models

We study the idea of the Higgs as a pseudo-Goldstone boson within the framework of partial supersymmetry in Randall-Sundrum scenarios and their CFT duals. The Higgs and third generation of the MSSM are composites arising from a strongly coupled supersymmetric CFT with global symmetry SO(5) spontaneously broken to SO(4), whilst the light generations and gauge fields are elementary degrees of freedom whose couplings to the strong sector explicitly break the global symmetry as well as supersymmetry. The presence of supersymmetry in the strong sector may allow the compositeness scale to be raised to ~10 TeV without fine tuning, consistent with the bounds from precision electro-weak measurements and flavour physics. The supersymmetric flavour problem is also solved. At low energies, this scenario reduces to the "More Minimal Supersymmetric Standard Model" where only stops, Higgsinos and gauginos are light and within reach of the LHC.Comment: 28 pages. v2 minor changes and Refs. adde