Inherent symmetry of a quantum system may protect its otherwise fragile states. Leveraging such protection requires testing its robustness against uncontrolled environmental interactions. Using 47 ...superconducting qubits, we implement the one-dimensional kicked Ising model, which exhibits nonlocal Majorana edge modes (MEMs) with
ℤ
2
parity symmetry. We find that any multiqubit Pauli operator overlapping with the MEMs exhibits a uniform late-time decay rate comparable to single-qubit relaxation rates, irrespective of its size or composition. This characteristic allows us to accurately reconstruct the exponentially localized spatial profiles of the MEMs. Furthermore, the MEMs are found to be resilient against certain symmetry-breaking noise owing to a prethermalization mechanism. Our work elucidates the complex interplay between noise and symmetry-protected edge modes in a solid-state environment.
Tough edges
The dynamics of quantum many-body systems can be profoundly affected by their interaction with the environment. This includes systems that have topological protection from certain kinds of perturbations due to symmetry. Mi
et al
. studied the interplay between symmetry and noise using a chain of 47 superconducting qubits. They implemented a periodically driven transverse Ising spin model, and found that the system’s edge modes were surprisingly resilient to some types of symmetry-breaking noise. —JS
A 47-qubit chain was used to study the interplay of noise and symmetry in an open quantum system.
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► First assembly of
Toxoplasma gondii isolates from wildlife from North America. ►
T. gondii DNA from 168 samples characterised by 11 PCR-RFLP markers. ► Twenty-two genotypes, ...including Types II and III, and 20 atypical genotypes found. ► Most
Toxoplasma gondii isolates were newly recognised clonal Type 12.
Little is known of the genetic diversity of
Toxoplasma gondii circulating in wildlife. In the present study wild animals, from the USA were examined for
T. gondii infection. Tissues of naturally exposed animals were bioassayed in mice for isolation of viable parasites. Viable
T. gondii was isolated from 31 animals including, to our knowledge for the first time, from a bald eagle (
Haliaeetus leucocephalus), five gray wolves (
Canis lupus), a woodrat (
Neotoma micropus), and five Arctic foxes
(Alopex lagopus). Additionally, 66
T. gondii isolates obtained previously, but not genetically characterised, were revived in mice.
Toxoplasma gondii DNA isolated from these 97 samples (31
+
66) was characterised using 11 PCR-restriction fragment length polymorphism (RFLP) markers (SAG1, 5′- and 3′-SAG2, alt.SAG2, SAG3, BTUB, GRA6, c22–8, c29–2, L358, PK1 and Apico). A total of 95 isolates were successfully genotyped. In addition to clonal Types II, and III, 12 different genotypes were found. These genotype data were combined with 74
T. gondii isolates previously characterised from wildlife from North America and a composite data set of 169 isolates comprised 22 genotypes, including clonal Types II, III and 20 atypical genotypes. Phylogenetic network analysis showed limited diversity with dominance of a recently designated fourth clonal type (Type 12) in North America, followed by the Type II and III lineages. These three major lineages together accounted for 85% of strains in North America. The Type 12 lineage includes previously identified Type A and X strains from sea otters. This study revealed that the Type 12 lineage accounts for 46.7% (79/169) of isolates and is dominant in wildlife of North America. No clonal Type I strain was identified among these wildlife isolates. These results suggest that
T. gondii strains in wildlife from North America have limited diversity, with the occurrence of only a few major clonal types.
By using a dry etch chemistry which relies on the highly preferential etching of silicon, over that of gallium (Ga), we show resist-free fabrication of precision, high aspect ratio nanostructures and ...microstructures in silicon using a focused ion beam (FIB) and an inductively coupled plasma reactive ion etcher (ICP-RIE). Silicon etch masks are patterned via Ga(+) ion implantation in a FIB and then anisotropically etched in an ICP-RIE using fluorinated etch chemistries. We determine the critical areal density of the implanted Ga layer in silicon required to achieve a desired etch depth for both a Pseudo Bosch (SF(6)/C(4)F(8)) and cryogenic fluorine (SF(6)/O(2)) silicon etching. High fidelity nanoscale structures down to 30 nm and high aspect ratio structures of 17:1 are demonstrated. Since etch masks may be patterned on uneven surfaces, we utilize this lithography to create multilayer structures in silicon. The linear selectivity versus implanted Ga density enables grayscale lithography. Limits on the ultimate resolution and selectivity of Ga lithography are also discussed.
An electromagnetic position tracking device was evaluated to determine its static and dynamic accuracy and reliability for applications related to measuring in vivo joint kinematics. The device ...detected the position and orientation of small coiled sensors, maintained in an electromagnetic field. System output was measured against known translations or rotations throughout the measurement volume. Average translational errors during static testing were 0.1±0.04, 0.2±0.17, and 0.8±0.81
mm (mean±SD) for sensors 50, 300, and 550
mm away from the field generator, respectively. Average rotational errors were 0.4±0.31°, 0.4±0.21°, and 0.9±0.85° (mean±SD) for sensors located at the same distances. Since we intended to use this system in an animal walking on a treadmill, we incrementally moved the sensors under various treadmill conditions. The effects of treadmill operation on translational accuracy were found to be negligible. The effects of dynamic motions on sensor-to-sensor distance were also assessed for future data collection in the animal. Sensor-to-sensor distance showed standard deviations of 2.6
mm and a range of 13
mm for the highest frequency tested (0.23
Hz). We conclude that this system is useful for static or slow dynamic motions, but is of limited use for obtaining gait kinematics at higher speeds.
Oxidative stress is a significant contributing factor in the pathogenesis of alcoholic liver disease (ALD). In the murine models of chronic alcohol consumption, induction of oxidative stress results ...in increased peroxidation of polyunsaturated fatty acids to form highly reactive electrophilic α/β unsaturated aldehydes that post-translationally modify proteins altering activity. Data are presented here suggesting that oxidative stress and the resulting carbonylation of hepatic proteins is an ongoing process involved in alcohol-induced cirrhosis.
Using age-matched pooled hepatic tissue obtained from healthy humans and patients with end stage cirrhotic ALD, overall carbonylation was assessed by immunohistochemistry and LC-MS/MS of streptavidin purified hepatic whole cell extracts treated with biotin hydrazide. Identified carbonylated proteins were further evaluated using bioinformatics analyses.
Using immunohistochemistry and Western blotting, protein carbonylation was increased in end stage ALD occurring primarily in hepatocytes. Mass spectrometric analysis revealed a total of 1224 carbonylated proteins in normal hepatic and end-stage alcoholic cirrhosis tissue. Of these, 411 were unique to cirrhotic ALD, 261 unique to normal hepatic tissue and 552 common to both groups. Bioinformatic pathway analysis of hepatic carbonylated proteins revealed a propensity of long term EtOH consumption to increase post-translational carbonylation of proteins involved in glutathione homeostatic, glycolytic and cytoskeletal pathways. Western analysis revealed increased expression of GSTA4 and GSTπ in human ALD. Using LC-MS/MS analysis, a nonenaldehyde post-translational modification was identified on Lysine 235 of the cytoskeletal protein vimentin in whole cell extracts prepared from human end stage ALD hepatic tissue. Conclusions: These studies are the first to use LC-MS/MS analysis of carbonylated proteins in human ALD and begin exploring possible mechanistic links with end-stage alcoholic cirrhosis and oxidative stress.
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•We demonstrate increased production of reactive aldehydes in human ALD.•Using LC-MS/MS we identify 411 carbonylated proteins unique to human ALD.•Pathway analysis revealed a propensity for adduction of GSH homeostatic proteins.•Using MS/MS, a nonenaldehyde adduct was identified on vimentin residue Lys235.•Reactive aldehyde modification of proteins contributes to pathogenesis of human ALD.
Bioreactors precondition tissue-engineered constructs (TECs) to improve integrity and hopefully repair. In this paper, we use functional tissue engineering to suggest criteria for preconditioning ...TECs. Bioreactors should (1) control environment during mechanical stimulation; (2) stimulate multiple constructs with identical or individual waveforms; (3) deliver precise displacements, including those that mimic in vivo activities of daily living (ADLs); and (4) adjust displacement patterns based on reaction loads and biological activity. We apply these criteria to three bioreactors. We have placed a pneumatic stimulator in a conventional incubator and stretched four constructs in each of five silicone dishes. We have also programmed displacement-limited stimuli that replicate frequencies and peak in vivo patellar tendon (PT) strains. Cellular activity can be monitored from spent media. However, our design prevents direct TEC force measurement. We have improved TEC stiffness as well as PT repair stiffness and shown correlations between the two. We have also designed an incubator to fit within each of two electromagnetic stimulators. Each incubator provides cell viability like a commercial incubator. Multiple constructs are stimulated with precise displacements that can mimic ADL strain patterns and record individual forces. Future bioreactors could be further improved by controlling and measuring TEC displacements and forces to create more functional tissues for surgeons and their patients.
In the liver, a contributing factor in the pathogenesis of non-alcoholic fatty liver disease (NASH) is oxidative stress, which leads to the accumulation of highly reactive electrophilic α/β ...unsaturated aldehydes. The objective of this study was to determine the impact of NASH on protein carbonylation and antioxidant responses in a murine model.
Liver-specific phosphatase and tensin homolog (PTEN)-deletion mice (PTENLKO) or control littermates were fed a standard chow diet for 45-55 weeks followed by analysis for liver injury, oxidative stress and inflammation.
Histology and Picrosirius red-staining of collagen deposition within the extracellular matrix revealed extensive steatosis and fibrosis in the PTENLKO mice but no steatosis or fibrosis in controls. Increased steatosis and fibrosis corresponded with significant increases in inflammation. PTEN-deficient livers showed significantly increased cell-specific oxidative damage, as detected by 4-hydroxy-2-nonenal (4-HNE) and acrolein staining. Elevated staining correlated with an increase in nuclear DNA repair foci (γH2A.X) and cellular proliferation index (Ki67) within zones 1 and 3, indicating oxidative damage was zonally restricted and was associated with increased DNA damage and cell proliferation. Immunoblots showed that total levels of antioxidant response proteins induced by nuclear factor erythroid-2-like-2 (Nrf2), including GSTμ, GSTπ and CBR1/3, but not HO-1, were elevated in PTENLKO as compared to controls, and IHC showed this response also occurred only in zones 1 and 3. Furthermore, an analysis of autophagy markers revealed significant elevation of p62 and LC3II expression. Mass spectrometric (MS) analysis identified significantly more carbonylated proteins in whole cell extracts prepared from PTENLKO mice (966) as compared to controls (809). Pathway analyses of identified proteins did not uncover specific pathways that were preferentially carbonylated in PTENLKO livers but, did reveal specific strongly increased carbonylation of thioredoxin reductase and of glutathione-S-transferases (GST) M6, O1, and O2.
Results show that disruption of PTEN resulted in steatohepatitis, fibrosis and caused hepatic induction of the Nrf2-dependent antioxidant system at least in part due to elevation of p62. This response was both cell-type and zone specific. However, these responses were insufficient to mitigate the accumulation of products of lipid peroxidation.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Thioredoxin reductase-1 (TrxR1)-, glutathione reductase (Gsr)-, and Nrf2 transcription factor-driven antioxidant systems form an integrated network that combats potentially carcinogenic oxidative ...damage yet also protects cancer cells from oxidative death. Here we show that although unchallenged wild-type (WT), TrxR1-null, or Gsr-null mouse livers exhibited similarly low DNA damage indices, these were 100-fold higher in unchallenged TrxR1/Gsr–double-null livers. Notwithstanding, spontaneous cancer rates remained surprisingly low in TrxR1/Gsr-null livers. All genotypes, including TrxR1/Gsr-null, were susceptible to N-diethylnitrosamine (DEN)-induced liver cancer, indicating that loss of these antioxidant systems did not prevent cancer cell survival. Interestingly, however, following DEN treatment, TrxR1-null livers developed threefold fewer tumors compared with WT livers. Disruption of TrxR1 in a marked subset of DEN-initiated cancer cells had no effect on their subsequent contributions to tumors, suggesting that TrxR1-disruption does not affect cancer progression under normal care, but does decrease the frequency of DEN-induced cancer initiation. Consistent with this idea, TrxR1-null livers showed altered basal and DEN-exposed metabolomic profiles compared with WT livers. To examine how oxidative stress influenced cancer progression, we compared DEN-induced cancer malignancy under chronically low oxidative stress (TrxR1-null, standard care) vs. elevated oxidative stress (TrxR1/Gsr-null livers, standard care or phenobarbital-exposed TrxR1-null livers). In both cases, elevated oxidative stress was correlated with significantly increased malignancy. Finally, although TrxR1-null and TrxR1/Gsr-null livers showed strong Nrf2 activity in noncancerous hepatocytes, there was no correlation between malignancy and Nrf2 expression within tumors across genotypes. We conclude that TrxR1, Gsr, Nrf2, and oxidative stress are major determinants of liver cancer but in a complex, context-dependent manner.
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