Atypical pitch processing is a feature of Autism Spectrum Disorder (ASD), which affects non-tone language speakers’ communication. Lifelong auditory experience has been demonstrated to modify ...genetically-predisposed risks for pitch processing. We examined individuals with ASD to test the hypothesis that lifelong auditory experience in tone language may eliminate impaired pitch processing in ASD. We examined children’s and adults’ Frequency-following Response (FFR), a neurophysiological component indexing early neural sensory encoding of pitch. Univariate and machine-learning-based analytics suggest less robust pitch encoding and diminished pitch distinctions in the FFR from individuals with ASD. Contrary to our hypothesis, results point to a linguistic pitch encoding impairment associated with ASD that may not be eliminated even by lifelong sensory experience.
Because RNA lacks strong intrinsic fluorescence, it has proven challenging to track RNA molecules in real time. To address this problem and to allow the purification of fluorescently tagged RNA ...complexes, we have selected a high affinity RNA aptamer called RNA Mango. This aptamer binds a series of thiazole orange (fluorophore) derivatives with nanomolar affinity, while increasing fluorophore fluorescence by up to 1,100-fold. Visualization of RNA Mango by single-molecule fluorescence microscopy, together with injection and imaging of RNA Mango/fluorophore complex in C. elegans gonads demonstrates the potential for live-cell RNA imaging with this system. By inserting RNA Mango into a stem loop of the bacterial 6S RNA and biotinylating the fluorophore, we demonstrate that the aptamer can be used to simultaneously fluorescently label and purify biologically important RNAs. The high affinity and fluorescent properties of RNA Mango are therefore expected to simplify the study of RNA complexes.
The limitations of current anti-angiogenic therapies necessitate other targets with complimentary mechanisms. Here, we show for the first time that soluble E-cadherin (sE-cad) (an 80-kDa soluble ...form), which is highly expressed in the malignant ascites of ovarian cancer patients, is a potent inducer of angiogenesis. In addition to ectodomain shedding, we provide further evidence that sE-cad is abundantly released in the form of exosomes. Mechanistically, sE-cad-positive exosomes heterodimerize with VE-cadherin on endothelial cells and transduce a novel sequential activation of β-catenin and NFκB signaling. In vivo and clinical data prove the relevance of sE-cad-positive exosomes for malignant ascites formation and widespread peritoneal dissemination. These data advance our understanding of the molecular regulation of angiogenesis in ovarian cancer and support the therapeutic potential of targeting sE-cad. The exosomal release of sE-cad, which represents a common route for externalization in ovarian cancer, could potentially be biomarkers for diagnosis and prognosis.
Leptoquarks extending the Standard Model (SM) have attracted increased attention in the recent literature. Hence, the identification of four-dimensional (4D) SM-like models and the classification of ...allowed leptoquarks from strings is an important step in the study of string phenomenology. We perform the most extensive search for SM-like models from the nonsupersymmetric heterotic string SO ( 16 ) × SO ( 16 ) , resulting in more than 170 000 inequivalent promising string models from 138 Abelian toroidal orbifolds. We explore the 4D massless particle spectra of these models in order to identify all exotics beside the three generations of quarks and leptons. Hereby, we learn which leptoquark can be realized in this string setup. Moreover, we analyze the number of SM Higgs doublets which is generically larger than one. Then, we identify SM-like models with a minimal particle content. These so-called almost SM models appear most frequently in the orbifold geometries Z2 × Z4 (2,4) and (1,6). Finally, we apply machine learning to our data set in order to predict the orbifold geometry where a given particle spectrum is most likely to be found.
A
bstract
Eclectic flavor groups arising from string compactifications combine the power of modular and traditional flavor symmetries to address the flavor puzzle. This top-down scheme determines the ...representations and modular weights of all matter fields, imposing strict constraints on the structure of the effective potential, which result in controlled corrections. We study the lepton and quark flavor phenomenology of an explicit, potentially realistic example model based on a 𝕋
6
/ℤ
3
×
ℤ
3
orbifold compactification of the heterotic string that gives rise to an Ω(2) eclectic flavor symmetry. We find that the interplay of flavon alignment and the localization of the modulus in the vicinity of a symmetry-enhanced point leads to naturally protected fermion mass hierarchies, favoring normal-ordered neutrino masses arising from a see-saw mechanism. We show that our model can reproduce all observables in the lepton sector with a small number of parameters and deliver predictions for so far undetermined neutrino observables. Furthermore, we extend the fit to quarks and find that Kähler corrections are instrumental in obtaining a successful simultaneous fit to the quark and lepton sectors.
Recent reports of increased tolerance to artemisinin derivatives--the most recently adopted class of antimalarials--have prompted a need for new treatments. The spirotetrahydro-β-carbolines, or ...spiroindolones, are potent drugs that kill the blood stages of Plasmodium falciparum and Plasmodium vivax clinical isolates at low nanomolar concentration. Spiroindolones rapidly inhibit protein synthesis in P. falciparum, an effect that is ablated in parasites bearing nonsynonymous mutations in the gene encoding the P-type cation-transporter ATPase4 (PfATP4). The optimized spiroindolone NITD609 shows pharmacokinetic properties compatible with once-daily oral dosing and has single-dose efficacy in a rodent malaria model.
In this paper, we review and provide additional details about our progress on multilayer silicon nitride (SiN)-on-silicon (Si) integrated photonic platforms. In these platforms, one or more SiN ...waveguide layers are monolithically integrated onto a Si photonic layer. This paper focuses on the development of three-layer platforms for the O- and SCL-bands for very large-scale photonic integrated circuits requiring hundreds or thousands of waveguide crossings. Low-loss interlayer transitions and ultralow-loss waveguide crossings have been demonstrated, along with bilevel and trilevel grating couplers for fiber-to-chip coupling. The SiN and Si passive devices have been monolithically integrated with high-efficiency optical modulators, photodetectors, and thermal tuners in a single photonic platform.
Eclectic flavor groups Nilles, Hans Peter; Ramos-Sánchez, Saúl; Vaudrevange, Patrick K. S.
The journal of high energy physics,
02/2020, Volume:
2020, Issue:
2
Journal Article
Peer reviewed
Open access
A
bstract
The simultaneous study of top-down and bottom-up approaches to modular flavor symmetry leads necessarily to the concept of eclectic flavor groups. These are non-trivial products of modular ...and traditional flavor symmetries that exhibit the phenomenon of local flavor enhancement in moduli space. We develop methods to determine the eclectic flavor groups that can be consistently associated with a given traditional flavor symmetry. Applying these methods to a large family of prominent traditional flavor symmetries, we try to identify potential candidates for realistic eclectic flavor groups and show that they are relatively rare. Model building with finite modular flavor symmetries thus appears to be much more restrictive than previously thought.
A
bstract
To obtain a unified framework for symmetric and asymmetric heterotic orbifold constructions we provide a systematic study of Narain compactifications orbifolded by finite order
T
-duality ...subgroups. We review the generalized vielbein that parametrizes the Narain moduli space (i.e. the metric, the
B
-field and the Wilson lines) and introduce a convenient basis of generators of the heterotic
T
-duality group. Using this we generalize the space group description of orbifolds to Narain orbifolds. This yields a unified, crystallographic description of the orbifold twists, shifts as well as Narain moduli. In particular, we derive a character formula that counts the number of unfixed Narain moduli after orbifolding. More-over, we develop new machinery that may ultimately open up the possibility for a full classification of Narain orbifolds. This is done by generalizing the geometrical concepts of
and affine classes from the theory of crystallography to the Narain case. Finally, we give a variety of examples illustrating various aspects of Narain orbifolds, including novel
T
-folds.
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