Cavity Optomechanical Sensing and Manipulation of an Atomic Persistent Current.

This theoretical work initiates contact between two frontier disciplines of physics, namely, atomic superfluid rotation and cavity optomechanics. It considers an annular Bose-Einstein condensate, which exhibits dissipationless flow and is a paradigm of rotational quantum physics, inside a cavity excited by optical fields carrying orbital angular momentum. It provides the first platform that can sense ring Bose-Einstein condensate rotation with minimal destruction, in situ and in real time, unlike demonstrated techniques, all of which involve fully destructive measurement. It also shows how light can actively manipulate rotating matter waves by optomechanically entangling persistent currents. Our work opens up a novel and useful direction in the sensing and manipulation of atomic superflow.

Effect of dermatological consultation on survival in patients with checkpoint inhibitor-associated cutaneous toxicity.

BACKGROUND: Cutaneous immune-related adverse events (cirAEs) are a common side-effect of immune checkpoint inhibitors (ICIs). However, prior work examining these toxicities in detail has considered only the fraction of events evaluated by dermatologists. Associations between dermatology referral, cirAE treatment and survival outcomes remain underexplored across care settings. OBJECTIVES: To comprehensively categorize cirAE patterns among all patients treated with immunotherapy at our institution, and to evaluate: (i) the effect of dermatology referral on cirAE treatment and (ii) the impact of cirAE treatment on survival. METHODS: This was a retrospective cohort analysis of patients with cancer who initiated ICI therapy between 1 January 2016 and 8 March 2019 and developed one or more cirAEs, as screened for using International Classification of Diseases 10th revision codes and confirmed via manual chart review (n = 358). All relevant information documented prior to 31 March 2020 was included. RESULTS: CirAEs evaluated by dermatologists were significantly more likely to be treated than cirAEs that were not referred (odds ratio 6·08, P < 0·001). Patients who received any cirAE treatment had improved progression-free survival [hazard ratio (HR) 0·59, P = 0·001] and overall survival (HR 0·58, P = 0·007) compared with those who did not. CONCLUSIONS: CirAEs evaluated by dermatologists were significantly more likely to be treated than cirAEs that were not referred, and patients who received any treatment for a cirAE had improved survival outcomes.

Cooperative light scattering from helical-phase-imprinted atomic rings.

We theoretically investigate the light scattering of super- and subradiant states of an atomic ring prepared by single excitation with a photon which carries an orbital angular momentum (OAM). For excitations with linear polarizations, the helical phase imprinted (HPI) atomic ring presents a discrete C4 rotational symmetry when number of atoms N = 4n with integers n, while for circular polarizations with arbitrary N, the continuous and C N symmetries emerge for the super- and subradiant modes, respectively. The HPI superradiant modes predominantly scatter photons in the forward-backward direction, and the forward scattering can be further enhanced as atomic rings are stacked along the excitation direction. The HPI subradiant modes then preferentially scatter photons in the transversal directions, and when rings are stacked concentrically and on a plane, crossover from sub- to superradiance is observed which leads to splitting and localization of the far-field scattering patterns in the polar angle. The HPI super- and subradiant states are thus detectable through measuring the far-field radiation patterns, which further allow quantum storage and detection of a single photon with an OAM.

Rotating Atomic Quantum Gases with Light-Induced Azimuthal Gauge Potentials and the Observation of the Hess-Fairbank Effect.

We demonstrate synthetic azimuthal gauge potentials for Bose-Einstein condensates from engineering atom-light couplings. The gauge potential is created by adiabatically loading the condensate into the lowest energy Raman-dressed state, achieving a coreless vortex state. The azimuthal gauge potentials act as effective rotations and are tunable by the Raman coupling and detuning. We characterize the spin textures of the dressed states, in agreements with the theory. The lowest energy dressed state is stable with a 4.5-s half-atom-number-fraction lifetime. In addition, we exploit the azimuthal gauge potential to demonstrate the Hess-Fairbank effect, the analogue of Meissner effect in superconductors. The atoms in the absolute ground state has a zero quasiangular momentum and transits into a polar-core vortex when the synthetic magnetic flux is tuned to exceed a critical value. Our demonstration serves as a paradigm to create topological excitations by tailoring atom-light interactions where both types of SO(3) vortices in the |⟨F[over →]⟩|=1 manifold, coreless vortices and polar-core vortices, are created in our experiment. The gauge field in the stationary Hamiltonian opens a path to investigating rotation properties of atomic superfluids under thermal equilibrium.

Randomised clinical trial: the efficacy and safety of oltipraz, a liver X receptor alpha-inhibitory dithiolethione in patients with non-alcoholic fatty liver disease.

BACKGROUND: Oltipraz is a synthetic dithiolethione with an antisteatotic effect by inhibiting the activity of liver X receptor alpha (LXR-α). Recent studies demonstrated the disruptive role of oltipraz on LXR-α-dependent lipogenesis in hepatocytes and a high-fat diet mouse model. AIM: To evaluate the efficacy and safety of oltipraz for reducing liver fat in subjects with non-alcoholic fatty liver disease (NAFLD). METHODS: We performed a multicentre, double-blind, placebo-controlled, phase II study. Subjects with a liver fat >20% and hypertransaminasemia were randomised to the three groups: placebo (n = 22), 30 mg of oltipraz (n = 22) or 60 mg of oltipraz (n = 24) twice daily for 24 weeks. Changes in the liver fat from baseline to 24 weeks quantified using magnetic resonance spectroscopy were the primary outcome. RESULTS: Compared with the placebo group (-3.2 ± 11.1%), absolute changes in the liver fat content increased in a dose-dependent manner: -7.7 ± 7.0% and -13.9 ± 10.7% for the low-dose and high-dose groups (P = 0.13 and P < 0.01). Per cent reduction in the liver fat content was also significantly greater in the high-dose group than in the placebo group (-34.6 ± 29.4% vs. -0.6 ± 62.9%, P = 0.046). Body mass indices (-1.0 ± 0.9% vs. -0.5 ± 1.4%, P = 0.04) significantly decreased in the high-dose group compared to the placebo group. However, absolute changes in insulin resistance, liver enzymes, lipids and cytokines were not significantly different among groups. The incidence of adverse events was comparable among groups. CONCLUSIONS: Twenty-four-week oltipraz treatment significantly reduced the liver fat content in patients with NAFLD. Clinicaltrials.gov (NCT01373554).

PHRF1 promotes genome integrity by modulating non-homologous end-joining.

Methylated histone readers are critical for chromatin dynamics, transcription, and DNA repair. Human PHRF1 contains a plant homeodomain (PHD) that recognizes methylated histones and a RING domain, which ubiquitinates substrates. A recent study reveals that PHRF1 is a tumor suppressor that promotes TGF-ß cytostatic signaling through TGIF ubiquitination. Also, PHRF1 is a putative phosphorylation substrate of ataxia telangiectasia-mutated/ataxia telangiectasia and Rad3-related kinases; however, the role of PHRF1 in DNA damage response is unclear. Here we report a novel function of PHRF1 in modulating non-homologous end-joining (NHEJ). PHRF1 quickly localizes to DNA damage lesions upon genotoxic insults. Ablation of PHRF1 decreases the efficiency of plasmid-based end-joining, whereas PHRF1 overexpression leads to an elevated NHEJ in H1299 reporter cells. Immunoprecipitation and peptide pull-down assays verify that PHRF1 constitutively binds to di- and trimethylated histone H3 lysine 36 (H3K36) (H3K36me2 and H3K36me3) via its PHD domain. Substitution of S915DT917E to ADAE in PHRF1 decreases its affinity for NBS1. Both PHD domain and SDTE motif are required for its NHEJ-promoting activity. Furthermore, PHRF1 mediates PARP1 polyubiquitination for proteasomal degradation. These results suggest that PHRF1 may combine with H3K36 methylation and NBS1 to promote NHEJ and stabilize genomic integrity upon DNA damage insults.

Clinical characterization and molecular classification of 12 Korean patients with pseudohypoparathyroidism and pseudopseudohypoparathyroidism.

CONTEXT: Pseudohypoparathyroidism (PHP) is defined as resistance toward parathyroid hormones. PHP and pseudopseudohypoparathyroidism (PPHP) are rare disorders resulting from genetic and epigenetic aberrations within or upstream of the GNAS locus. This study investigated the clinical characteristics and performed a molecular analysis of PHP and PPHP. METHODS: A total of 12 patients with (P)PHP from 11 unrelated families (4 with PHP-Ia, 6 with PHP-Ib, and 2 with PPHP) were characterized using both clinical and molecular methods. Clinical features included the presenting symptoms, Albright hereditary osteodystrophy features, and resistance to hormones. Comprehensive analysis of the GNAS and STX16 loci was undertaken to investigate the molecular defects underlying (P)PHP. RESULTS: All PHP-Ib patients displayed hypocalcemic symptoms. All PHP-Ia patients showed resistance toward TSH, in addition to PTH. In most patients with PHP, when the diagnosis of PHP was first established, hypocalcemia and hyperphosphatemia were associated with a significant increase in serum PTH levels. One patient with PHP-Ia was diagnosed with growth hormone deficiency and showed a good response to human recombinant growth hormone therapy. 6 patients with PHP-Ia and PPHP showed 5 different mutations in the GNAS gene. 5 patients with PHP-Ib displayed a loss of differentially methylated region (DMR) imprints of the maternal GNAS. One PHP-Ib patient showed a de novo microdeletion in STX16 and a loss of methylation of exon A/B on the maternal allele. No patients revealed paternal disomy among 4 patients with PHP-Ib. CONCLUSIONS: Identification of the molecular causes of PHP and PPHP explains their distinctive clinical features and enables confirmation of the diagnosis and exact genetic counseling.

A hypoxia-dependent upregulation of hypoxia-inducible factor-1 by nuclear factor-κB promotes gastric tumour growth and angiogenesis.

BACKGROUND: The underlying mechanisms involved in the activation of hypoxia-inducible factor-1 (HIF-1) in gastric cancer remain unclear. As nuclear factor-κB (NF-κB) as well as HIF-1 have been implicated in angiogenesis of various cancers, we investigated their relationship in gastric cancer. METHODS: Nuclear expressions of HIF-1α and NF-κB/RelA were assessed in 251 human gastric carcinoma specimens by immunohistochemical tissue array analysis. Stable human gastric cancer cells, infected with a retroviral vector containing super-suppressive mutant form of IκBα (IκBαM), were used for animal studies as well as cell culture experiments. Xenografted tumours were measured and IκBαM effects on angiogenesis and HIF-1α activation were assessed by immunohistochemistry, western blotting, luciferase reporter assay, and semiquantitative reverse transcription-polymerase chain reaction. In addition, NF-κB effects on the HIF-1α degradation and synthesis were examined. RESULTS: Hypoxia-inducible factor-1α activation positively correlated with RelA activation in clinical gastric cancer samples (P<0.001). The IκBαM overexpression suppressed tumour growth, microvessel density, and HIF-1α activation in xenografted tumours. Cell culture experiments showed that hypoxia-induced HIF-1α expression was reduced by NF-κB inhibition under hypoxic conditions at the translational level. CONCLUSION: The hypoxia-dependent activation of the NF-κB/HIF-1α/VEGF pathway contributes, at least in part, to gastric cancer promotion via enhancement of angiogenesis.

Quantum simulation of frustrated Ising spins with trapped ions.

A network is frustrated when competing interactions between nodes prevent each bond from being satisfied. This compromise is central to the behaviour of many complex systems, from social and neural networks to protein folding and magnetism. Frustrated networks have highly degenerate ground states, with excess entropy and disorder even at zero temperature. In the case of quantum networks, frustration can lead to massively entangled ground states, underpinning exotic materials such as quantum spin liquids and spin glasses. Here we realize a quantum simulation of frustrated Ising spins in a system of three trapped atomic ions, whose interactions are precisely controlled using optical forces. We study the ground state of this system as it adiabatically evolves from a transverse polarized state, and observe that frustration induces extra degeneracy. We also measure the entanglement in the system, finding a link between frustration and ground-state entanglement. This experimental system can be scaled to simulate larger numbers of spins, the ground states of which (for frustrated interactions) cannot be simulated on a classical computer.

Eruptive pseudo-angiomatosis lesions are associated with intravascular neutrophils and do not harbour Epstein-Barr virus.

BACKGROUND: Eruptive pseudo-angiomatosis (EPA) is a rare, relatively newly described cutaneous disorder characterized by the sudden onset of several bright red, angioma-like papules surrounded by blanched halo. Its aetiology is unknown; however, viral infection or mosquito bites have been speculated as possible causes. OBJECTIVE: This study aims to determine the clinical and histopathological features of EPA, and whether it is associated with Epstein-Barr virus (EBV) infection. METHODS: We conducted a retrospective chart review of 25 EPA cases from 2006 to 2008. In order to determine latent EBV infection, EBV-encoded small RNA (EBER) in situ hybridization was performed in 18 subjects. To determine EPA's distinguishing histological characteristics, we compared the cases with 22 control cases of perivascular lymphocytic infiltration for haematoxylin and eosin, CD3, CD4, CD8, CD31 and c-kit staining patterns. RESULTS: The patient sample's female-to-male ratio was 2.1 : 1, and the patients' age ranged from 5 to 79 years (average 46 years). The lesions appeared during the months of July to September in all but 3 patients. Skin biopsies demonstrated capillary ectasia with perivascular mononuclear cellular infiltrates in the upper dermis. Most patients were otherwise healthy, and routine laboratory results were all normal except in one patient who had diabetes. The skin lesions faded without any treatment in 1-2 weeks. Results of EBER in situ hybridization were all negative. The only histological distinguishing feature of EPA was the presence of intravascular neutrophils, which was found to be present in 19 of the 20 EPA cases (95%), in contrast to only 3 of the 22 control subjects (14%) (P < 0.0001). CONCLUSION: The sudden onset of lesions during the summer months among our patients supports the 'paraviral eruption' concept of this probably underdiagnosed condition. The significant presence of intravascular neutrophils may be a diagnostic clue of EPA in South Korea.

Entanglement and tunable spin-spin couplings between trapped ions using multiple transverse modes.

We demonstrate tunable spin-spin couplings between trapped atomic ions, mediated by laser forces on multiple transverse collective modes of motion. A sigma_{x}sigma_{x}-type Ising interaction is realized between quantum bits stored in the ground hyperfine clock states of ;{171}Yb;{+} ions. We demonstrate entangling gates and tailor the spin-spin couplings with two and three trapped ions. The use of closely spaced transverse modes provides a new class of interactions relevant to quantum computing and simulation with large collections of ions in a single crystal.

The effects of midazolam on the bispectral index after fetal expulsion in caesarean section under general anaesthesia with sevoflurane.

The effects of midazolam used with low concentration inhaled anaesthetics on the bispectral index (BIS) was investigated after fetal expulsion during caesarean section. Forty-five patients undergoing caesarean section received either normal saline (control, n = 15), or an intravenous bolus of 0.03 mg/kg (n = 15) or 0.05 mg/kg (n = 15) midazolam. Changes in BIS and maternal haemodynamics were monitored before induction, on intubation, at uterine incision, on delivery, at 3, 5 and 10 min after fetal expulsion, at subcutaneous tissue closure, at skin closure, on eye opening and at extubation. BIS values in the group that received 0.05 mg/kg midazolam were significantly lower than in the other two groups at 3, 5 and 10 min after fetal expulsion, and at subcutaneous tissue closure and skin closure. Values of BIS < 60 could only be maintained with 0.05 mg/kg midazolam and there was no delay in maternal emergence or recovery.

Accuracy of corneal flap thickness achieved by two different age MK-2000 microkeratomes.

AIMS: To investigate the accuracy of corneal flap thickness (FT) using two different age MK-2000 microkeratomes. METHODS: The prospective cohort study enroled 260 patients with refractive error. Flaps were created using two microkeratomes A and B (new and aged, respectively) with 130-mum heads in two patient groups and two times the same blade in both treated eyes of each patient. The variations in FTs were compared between two groups and between both operated eyes of each patient. The correlations were analysed between FT and CCT or keratometric power. RESULTS: In the A and B groups, the average FTs were 123.3+/-18.7 and 147.5+/-19.1 mum respectively. Difference in measurements between the actual FTs of first eye operations in the A group and intended 130 mum of FTs was not significant (P=0.462), but those of second operated eyes in the A group and both treated eyes in the B group were significant (P<0.001). Second cut achieved a thinner flap and increased the variability in FT, and an aged microkeratome achieved a thicker flap than a new microkeratome and than that claimed by the manufacturer. Positive correlations were observed between preoperative CCT and FT (P<0.05). CONCLUSIONS: The first eye operation by a new MK-2000 microkeratome achieves the accuracy of the intended FT. FTs varied between first and second cuts of each patient and between two different age MK-2000 microkeratomes. LASIK surgeons should compare FT when using an aged MK-2000 microkeratome, and frequent and periodic comparison of FT achieved by all microkeratomes may be also recommended.

A novel transcript of mouse interleukin-20 receptor acts on glomerular mesangial cells as an aggravating factor in lupus nephritis.

We identified a novel soluble protein, mouse (m)IL-20R1a, generated by alternative splicing of the mIL-20R1 gene, which encodes one subunit of the receptor complex for mIL-19, mIL-20 and mIL-24. mIL-20R1a has 77.14% amino-acid identity with the extracellular domain of mIL-20R1. However, no significant interaction between mIL-20R1a and mIL-19 or mIL-20 was detected. Consequently, we aimed to clarify whether mIL-20R1a might function as a novel effector on certain cells. Competitive binding assays demonstrated that mIL-20R1a bound to cell surfaces and resulted in AKT and JNK phosphorylation in primary mesangial cells (MCs) isolated from either the wild-type mice, DBA/W mice, or the SLE-prone mice, NZB/W mice. NZB/W MCs expressed more mIL-20R1a transcript than DBA/W MCs did. Furthermore, mIL-20R1a-treated NZB/W MCs produced higher level of chemokines, renal fibrogenic factors and ROS than mIL-20R1a-treated DBA/W MCs did. These factors are involved in the pathogenesis of lupus nephritis. Endogenous mIL-20R1a was upregulated in the bladder, colon and spleen tissue of NZB/W mice. Elevated mIL-20R1a in the spleen tissue of NZB/W mice was expressed mainly in monocytes and B cells. mIL-20R1a further induced mIL-10 production by the anti-IgM antibody-stimulated B cells in NZB/W mice. Therefore, mIL-20R1a-mediated effects may exacerbate the disease outcome of lupus nephritis.

Interleukin-20 induced cell death in renal epithelial cells and was associated with acute renal failure.

Acute renal failure is an abrupt decrease in renal function. Interleukin (IL)-10 inhibits ischemic and cisplatin-induced acute renal failure. We aimed to determine whether IL-20 affects renal tubular epithelial cells and is associated with acute renal failure. We analyzed the expression of IL-20 and its receptor (R) in the kidneys of rats with HgCl(2)-induced acute renal failure. Reverse transcription-PCR showed upregulated IL-20, and its receptors and immunohistochemical staining showed strongly expressed IL-20 protein in proximal tubular epithelial cells. We analyzed human proximal tubular epithelial (HK-2) cells, which expressed both IL-20 and its receptors. IL-20 specifically induced mitochondria-dependent apoptosis by activating caspase 9 in HK-2 cells. IL-20 also activated c-Jun N-terminal kinase and extracellular signal-regulated kinase 1/2, the downstream signals implicated in the apoptosis of HK-2 cells. Furthermore, IL-20 upregulated the transcripts of transforming growth factor (TGF)-beta1, a critical mediator of renal injury. In hypoxic HK-2 cells, IL-20 and IL-22R1 transcripts increased, and IL-20 upregulated IL-1 beta transcripts. In vivo study further demonstrated that anti-IL-20 antibody reduced the expression of TGF-beta1 and IL-1 beta and the number of damaged tubular cells in the kidneys of rats with acute renal failure. We concluded that IL-20 may be involved in the injury of renal epithelial cells in acute renal failure.

Effect of nicardipine on haemodynamic and bispectral index changes following endotracheal intubation.

We investigated the effect of IV nicardipine on haemodynamic and bispectral index responses to the induction of general anaesthesia and intubation. Forty patients were randomly allocated to two groups of 20 to receive normal saline or nicardipine 15 microg/kg IV 30 s after induction. Ninety seconds later, tracheal intubation was performed. Systolic blood pressure, heart rate and bispectral index were measured at baseline, 1 min after induction, pre-intubation, and every minute until 5 min after endotracheal intubation. Rate-pressure product values were calculated. In the nicardipine group, systolic blood pressure decreased compared with the control group, and heart rate increased comparedwith the control group. Bispectral index and rate-pressure product showed no differences between the two groups. In conclusion, the administration of 15 microg/kg nicardipine IV does not affect anaesthetic depth in response to the induction of general anaesthesia and intubation.