Idiopathic intracranial hypertension (IIH) is a disorder of elevated intracranial pressure of unknown cause occurring predominantly in young women of childbearing age. The typical patient symptom ...profile is the presence of daily headache, pulse synchronous tinnitus, transient visual obscurations, and papilledema with its associated visual loss. Although surgical procedures are performed for those who fail medical therapy, their relative efficacy remains unclear. The main morbidity of IIH is from visual loss. This visual loss is present in most patients and can usually be reversed if recognized early in the patients' course and treated.
Controllable arrays of ions and ultracold atoms can simulate complex many-body phenomena and may provide insights into unsolved problems in modern science. To this end, experimentally feasible ...protocols for quantifying the buildup of quantum correlations and coherence are needed, as performing full state tomography does not scale favourably with the number of particles. Here we develop and experimentally demonstrate such a protocol, which uses time reversal of the many-body dynamics to measure out-of-time-order correlation functions (OTOCs) in a long-range Ising spin quantum simulator with more than 100 ions in a Penning trap. By measuring a family of OTOCs as a function of a tunable parameter we obtain fine-grained information about the state of the system encoded in the multiple quantum coherence spectrum, extract the quantum state purity, and demonstrate the buildup of up to 8-body correlations. Future applications of this protocol could enable studies of many-body localization, quantum phase transitions, and tests of the holographic duality between quantum and gravitational systems.
The outbreak of the coronavirus disease 2019 (COVID-19) and its rapid global spread have created unprecedented challenges to health care systems. Significant and sustained efforts have focused on ...mobilization of personal protective equipment, intensive care beds, and medical equipment, while substantially less attention has focused on preserving the psychological health of the medical workforce tasked with addressing the challenges of the pandemic. And yet, similar to battlefield conditions, health care workers are being confronted with ongoing uncertainty about resources, capacities, and risks; as well as exposure to suffering, death, and threats to their own safety. These conditions are engendering high levels of fear and anxiety in the short term, and place individuals at risk for persistent stress exposure syndromes, subclinical mental health symptoms, and professional burnout in the long term. Given the potentially wide-ranging mental health impact of COVID-19, protecting health care workers from adverse psychological effects of the pandemic is critical. Therefore, we present an overview of the potential psychological stress responses to the COVID-19 crisis in medical providers and describe preemptive resilience-promoting strategies at the organizational and personal level. We then describe a rapidly deployable Psychological Resilience Intervention founded on a peer support model (Battle Buddies) developed by the United States Army. This intervention—the product of a multidisciplinary collaboration between the Departments of Anesthesiology and Psychiatry & Behavioral Sciences at the University of Minnesota Medical Center—also incorporates evidence-informed “stress inoculation” methods developed for managing psychological stress exposure in providers deployed to disasters. Our multilevel, resource-efficient, and scalable approach places 2 key tools directly in the hands of providers(1) a peer support Battle Buddy; and (2) a designated mental health consultant who can facilitate training in stress inoculation methods, provide additional support, or coordinate referral for external professional consultation. In parallel, we have instituted a voluntary research data-collection component that will enable us to evaluate the intervention’s effectiveness while also identifying the most salient resilience factors for future iterations. It is our hope that these elements will provide guidance to other organizations seeking to protect the well-being of their medical workforce during the pandemic. Given the remarkable adaptability of human beings, we believe that, by promoting resilience, our diverse health care workforce can emerge from this monumental challenge with new skills, closer relationships, and greater confidence in the power of community.
Quantum simulation of spin models can provide insight into problems that are difficult or impossible to study with classical computers. Trapped ions are an established platform for quantum ...simulation, but only systems with fewer than 20 ions have demonstrated quantum correlations. We studied quantum spin dynamics arising from an engineered, homogeneous Ising interaction in a two-dimensional array of ⁹Be⁺ ions in a Penning trap. We verified entanglement in spin-squeezed states of up to 219 ions, directly observing 4.0 ± 0.9 decibels of spectroscopic enhancement, and observed states with non-Gaussian statistics consistent with oversqueezed states. The good agreement with ab initio theory that includes interactions and decoherence lays the groundwork for simulations of the transverse-field Ising model with variable-range interactions, which are generally intractable with classical methods.
Cystinosis is a rare autosomal recessive lysosomal storage disease, associated with high morbidity and mortality. Mutations in the CTNS gene disable a membrane protein responsible for the transport ...of cystine out of the lysosome. Loss of transporter function leads to intralysosomal cystine accumulation and long-term damage to various tissues and organs, including the kidneys, eyes, liver, muscles, pancreas, and brain. The only cystine-depletion therapy for treatment of cystinosis is cysteamine which requires frequent administration of high doses and often causes gastrointestinal pain as well as pungent sulfurous odor in patients. The current in vitro study evaluated antioxidants, N-acetylcysteine amide (NACA; NPI-001) and (2R,2R')-3,3'-disulfanediyl bis(2-acetamidopropanamide) (diNACA; NPI-002), as potential treatments for cystinosis. Cytotoxicity of cysteamine, NACA and diNACA was evaluated in cultured human cystinotic fibroblasts (HCFs). HCFs were cultured in 96 well plates incubated for 0-72 h in the presence of 25, 50 or 75 muM each of either cysteamine, NACA or diNACA along with an untreated control. Media was removed and cell viability assessed. Next, cystine-depleting activities of cysteamine, NACA and diNACA were screened in HCFs cell culture utilizing an inexpensive, proven colorimetric assay. HCFs were seeded and allowed to reach approximately 80% confluence before the addition of the test articles: 50 muM of either cysteamine, NACA or diNACA in media along with an untreated control. HCFs were incubated, harvested, and cystine was reduced to cysteine, the concentration of which was then determined per quantity of protein compared to a cysteine standard. Statistically significant cystine depletion was determined by paired t-test versus untreated control (p < 0.05). Neither cysteamine, NACA nor diNACA at 25, 50 or 75 muM caused cytotoxicity in HCFs. Treatment with all tested concentrations (25, 50 or 75 microM) of either NACA or diNACA at 48 or 72 h resulted in statistically significant increases in cell viability, relative to untreated control, whereas the higher concentrations (50 or 75 microM) of cysteamine achieved statistical significance at both timepoints but not the lowest concentration (25 microM). All test articles depleted cystine from HCFs compared to control. NACA depletion of cystine was statistically superior to cysteamine at 6, 24 and 48 h and numerically greater at 72 h. DiNACA depletion of cystine was statistically superior to cysteamine at 6 and 48 h, slightly numerically greater at 24 h and slightly less at 72 h. NACA and diNACA were non cytotoxic to HCFs and significantly increased cell viability. Cystine reduction was determined as percent of control after incubation with 50 microM of NACA, diNACA or cysteamine in HCFs cell culture for 6, 24, 48 and 72 h. Of the three test articles, NACA exhibited most rapid and greatest potency in cystine reduction. Rank order potency for cystine reduction over time was observed, NACA > diNACA greater than or equai to cysteamine. Therefore, further study of NACA and diNACA as potential treatments for cystinosis is warranted.
We provide an exact construction of particular Hamitonians on a one-dimensional lattice as matrix product operators, a type of tensor network. Namely, we consider Hamiltonians describing interactions ...between degrees of freedom at lattice sites whose strength grows with the lattice site separation as a polynomial multiplied by an exponential. We show that the bond dimension is (k + 3) for a polynomial of order k, independent of the system size and the number of particles. Our construction is manifestly translationally invariant, and so may be used in finite- or infinite-size variational matrix product state algorithms. Our results provide new insight into the correlation structure of many-body quantum operators, and may also be practical in simulations of many-body systems whose interactions are exponentially screened at large distances, but may have complex short-distance structure.
We propose the use of optical lattice clocks operated with fermionic alkaline-earth atoms to study spin-orbit coupling (SOC) in interacting many-body systems. The SOC emerges naturally during the ...clock interrogation, when atoms are allowed to tunnel and accumulate a phase set by the ratio of the "magic" lattice wavelength to the clock transition wavelength. We demonstrate how standard protocols such as Rabi and Ramsey spectroscopy that take advantage of the sub-Hertz resolution of state-of-the-art clock lasers can perform momentum-resolved band tomography and determine SOC-induced s-wave collisions in nuclear-spin-polarized fermions. With the use of a second counterpropagating clock beam, we propose a method for engineering controlled atomic transport and study how it is modified by p- and s-wave interactions. The proposed spectroscopic probes provide clean and well-resolved signatures at current clock operating temperatures.
Heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) is a stress granule-associated RNA-binding protein that plays a role in apoptosis and cellular stress recovery. HnRNP A1 is a major non-histone ...target of protein arginine methyltransferase 1, which asymmetrically dimethylates hnRNP A1 at several key arginine residues within its arginine–glycine–glycine (RGG)-motif region. Although arginine methylation is known to regulate general RNA binding of hnRNP A1 in vitro, the functional role of arginine methylation in hnRNP A1 cytoplasmic activity is unknown. To test the impact of key methylarginine residues on hnRNP A1 cytoplasmic activity and stress granule association, cytoplasmically restricted Flag-tagged mutants of hnRNP A1 were generated in which key methylarginine residues within the RGG-motif region were changed to either lysine or alanine. Lysine substitution, which mimics unmethylated arginine, resulted in a 40% increase in internal ribosome entry site trans-acting factor (ITAF) activity and the protein readily associates with stress granules. Alanine substitution resulted in a loss of ITAF activity and reduced mRNA binding. The alanine mutant also displays reduced stress granule association and suppresses stress granule formation. Our data suggest that arginine residues within the RGG-motif region are critical for hnRNP A1 cytoplasmic activities and that endogenous asymmetric dimethylation of the RGG-motif region suppresses hnRNP A1 ITAF activity in cells. Our findings indicate that methylarginine residues within the RGG-motif region of hnRNP A1 are important for its cytoplasmic activities and that hypomethylation and/or mutation of the RGG-motif region may contribute to the role of hnRNP A1 in diseases such as cancer.
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•The functional role of asymmetric dimethylation within the hnRNP A1 RGG-motif region is unknown.•Lysine substitution within the RGG-motif region increases hnRNP A1 ITAF activity by 40%.•Asymmetric dimethylation of hnRNP A1 may serve to inhibit ITAF activity.•Alanine substitution within the RGG-motif region abolishes hnRNP A1 ITAF activity and mRNA-binding ability.•The hnRNP A1 alanine mutant inhibits stress granule formation in a dominant-negative manner.
We investigate an extension of the quantum Ising (QI) model in one spatial dimension including long-range 1 r interactions in its statics and dynamics with possible applications from heteronuclear ...polar molecules in optical lattices to trapped ions described by two-state spin systems. We introduce the statics of the system via both numerical techniques with finite size and infinite size matrix product states (MPSs) and a theoretical approaches using a truncated Jordan-Wigner transformation for the ferromagnetic and antiferromagnetic case and show that finite size effects have a crucial role shifting the quantum critical point of the external field by fifteen percent between thirty-two and around five-hundred spins. We numerically study the Kibble-Zurek hypothesis in the long-range QI model with MPSs. A linear quench of the external field through the quantum critical point yields a power-law scaling of the defect density as a function of the total quench time. For example, the increase of the defect density is slower for longer-range models and the critical exponent changes by twenty-five percent. Our study emphasizes the importance of such long-range interactions in statics and dynamics that could point to similar phenomena in a different setup of dynamical systems or for other models.
Huntington's disease (HD) is a devastating, genetic neurodegenerative disease caused by a tri-nucleotide expansion in exon 1 of the huntingtin gene. HD is clinically characterized by chorea, ...emotional and psychiatric disturbances and cognitive deficits with later symptoms including rigidity and dementia. Pathologically, the cortico-striatal pathway is severely dysfunctional as reflected by striatal and cortical atrophy in late-stage disease. Brain-derived neurotrophic factor (BDNF) is a neuroprotective, secreted protein that binds with high affinity to the extracellular domain of the tropomyosin-receptor kinase B (TrkB) receptor promoting neuronal cell survival by activating the receptor and down-stream signaling proteins. Reduced cortical BDNF production and transport to the striatum have been implicated in HD pathogenesis; the ability to enhance TrkB signaling using a BDNF mimetic might be beneficial in disease progression, so we explored this as a therapeutic strategy for HD. Using recombinant and native assay formats, we report here the evaluation of TrkB antibodies and a panel of reported small molecule TrkB agonists, and identify the best candidate, from those tested, for in vivo proof of concept studies in transgenic HD models.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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