Stabilization and operation of a Kerr-cat qubit.

Quantum superpositions of macroscopically distinct classical states-so-called Schrödinger cat states-are a resource for quantum metrology, quantum communication and quantum computation. In particular, the superpositions of two opposite-phase coherent states in an oscillator encode a qubit protected against phase-flip errors1,2. However, several challenges have to be overcome for this concept to become a practical way to encode and manipulate error-protected quantum information. The protection must be maintained by stabilizing these highly excited states and, at the same time, the system has to be compatible with fast gates on the encoded qubit and a quantum non-demolition readout of the encoded information. Here we experimentally demonstrate a method for the generation and stabilization of Schrödinger cat states based on the interplay between Kerr nonlinearity and single-mode squeezing1,3 in a superconducting microwave resonator4. We show an increase in the transverse relaxation time of the stabilized, error-protected qubit of more than one order of magnitude compared with the single-photon Fock-state encoding. We perform all single-qubit gate operations on timescales more than sixty times faster than the shortest coherence time and demonstrate single-shot readout of the protected qubit under stabilization. Our results showcase the combination of fast quantum control and robustness against errors, which is intrinsic to stabilized macroscopic states, as well as the potential of of these states as resources in quantum information processing5-8.

Quantum error correction of a qubit encoded in grid states of an oscillator.

The accuracy of logical operations on quantum bits (qubits) must be improved for quantum computers to outperform classical ones in useful tasks. One method to achieve this is quantum error correction (QEC), which prevents noise in the underlying system from causing logical errors. This approach derives from the reasonable assumption that noise is local, that is, it does not act in a coordinated way on different parts of the physical system. Therefore, if a logical qubit is encoded non-locally, we can-for a limited time-detect and correct noise-induced evolution before it corrupts the encoded information1. In 2001, Gottesman, Kitaev and Preskill (GKP) proposed a hardware-efficient instance of such a non-local qubit: a superposition of position eigenstates that forms grid states of a single oscillator2. However, the implementation of measurements that reveal this noise-induced evolution of the oscillator while preserving the encoded information3-7 has proved to be experimentally challenging, and the only realization reported so far relied on post-selection8,9, which is incompatible with QEC. Here we experimentally prepare square and hexagonal GKP code states through a feedback protocol that incorporates non-destructive measurements that are implemented with a superconducting microwave cavity having the role of the oscillator. We demonstrate QEC of an encoded qubit with suppression of all logical errors, in quantitative agreement with a theoretical estimate based on the measured imperfections of the experiment. Our protocol is applicable to other continuous-variable systems and, in contrast to previous implementations of QEC10-14, can mitigate all logical errors generated by a wide variety of noise processes and facilitate fault-tolerant quantum computation.

Gated Conditional Displacement Readout of Superconducting Qubits.

We have realized a new interaction between superconducting qubits and a readout cavity that results in the displacement of a coherent state in the cavity, conditioned on the state of the qubit. This conditional state, when it reaches the cavity-following, phase-sensitive amplifier, matches its measured observable, namely, the in phase quadrature. In a setup where several qubits are coupled to the same readout resonator, we show it is possible to measure the state of a target qubit with minimal dephasing of the other qubits. Our results suggest novel directions for faster readout of superconducting qubits and implementations of bosonic quantum error-correcting codes.

Axillary tumour burden in women with one abnormal node on ultrasound compared to women with multiple abnormal nodes.

AIM: To determine if the number of abnormal nodes seen on preoperative axillary ultrasound (AUS) is a predictor of the number of positive nodes at histology for women with needle-biopsy-proven positive nodes. MATERIALS AND METHODS: This prospective multicentre cohort study included consecutive patients with early breast cancer who had needle-biopsy-proven positive nodes on AUS and underwent axillary lymph node dissection (ALND) between October 2015 and July 2016. The number of abnormal nodes at preoperative AUS was recorded by breast radiologists or radiographers. RESULTS: One hundred and twenty-three patients were included in the study. The median age of the women was 62 (range 30-93) years. Fifty-four of the 123 (44%) women had one abnormal node, whereas 69 (56%) had multiple abnormal nodes on AUS. Forty of the 123 (33%) women had two or fewer nodes with metastases at histology after ALND. Tumours ≤20 mm (p<0.001) and one abnormal node on AUS (p<0.001) were associated with two or fewer nodes with metastases at ALND. Both remained significant in logistic regression analysis. The likelihood of at least three metastases based on the combination of these two factors had 95% sensitivity (79 of 83), 35% specificity (14 of 40), a negative predictive value of 78% (14 of 18), and a positive predictive value of 75% (79 of 105). CONCLUSION: Among women with needle-biopsy-proven positive nodes, around three in four women (78%) with an invasive tumour ≤2 cm and one abnormal node on AUS have two or fewer positive nodes at ALND. These women are overtreated by upfront ALND and can be offered sentinel node biopsy (SNB).

Synthesis and Evaluation of Chirally Defined Side Chain Variants of 7-Chloro-4-Aminoquinoline To Overcome Drug Resistance in Malaria Chemotherapy.

A novel 4-aminoquinoline derivative [(S)-7-chloro-N-(4-methyl-1-(4-methylpiperazin-1-yl)pentan-2-yl)-quinolin-4-amine triphosphate] exhibiting curative activity against chloroquine-resistant malaria parasites has been identified for preclinical development as a blood schizonticidal agent. The lead molecule selected after detailed structure-activity relationship (SAR) studies has good solid-state properties and promising activity against in vitro and in vivo experimental malaria models. The in vitro absorption, distribution, metabolism, and excretion (ADME) parameters indicate a favorable drug-like profile.

Broad spectrum anti-infective properties of benzisothiazolones and the parallels in their anti-bacterial and anti-fungal effects.

Various mono- and bis-benzisothiazolone derivatives were synthesized and screened against different strains of bacteria and fungi in order to understand the effect of multiple electrophilic sulfur atoms and substitution pattern in the immediate vicinity of reactive sulfur. Staphyllococcus aureus-ATCC 7000699, MRSA and S. aureus-ATCC 29213 (Quality Control strain) were more susceptible to this class of compounds, and the most potent derivative 1.15 had MIC50 of 0.4µg/mL (cf. Gentamicin=0.78µg/mL). CLogP value, optimally in the range of 2.5-3.5, appeared to contribute more to the activity than the steric and electronic effects of groups attached at nitrogen. By and large, their anti-fungal activities also followed a similar trend with respect to the structure and CLogP values. The best potency of IC50=0.1µg/mL was shown by N-benzyl derivative (1.7) against Aspergillus fumigatus; it was also potent against Candida albicans, Cryptococcus neoformans, Sporothrix schenckii, and Candida parapsilosis with IC50 values ranging from 0.4 to 1.3µg/mL. Preliminary studies also showed that this class of compounds have the ability to target malaria parasite with IC50 values in low micromolar range, and improvement of selectivity is possible through structure optimization.

Correlation between in vitro and in vivo antimalarial activity of compounds using CQ-sensitive and CQ-resistant strains of Plasmodium falciparum and CQ-resistant strain of P. yoelii.

Present efforts have been made to establish a correlation between in vitro and in vivo antimalarial activity using MIC, IC50 and IC90 values against CQ-sensitive (3D7) and CQ-resistant (K1) strains of Plasmodium falciparum and in vivo activity against Plasmodium yoelii. The method of discriminant function analysis (DFA) was applied to analyze the data. It was observed that in vitro IC90 values against both 3D7 and K1 strains (p < 0.001) have strong correlation with in vivo curative activity. The respective IC50 and IC90 values of compounds, which cured mice (i.e., animals did not show recrudescence of parasitemia even after 60 days posttreatment), ranged between 3 and 14 nM and 14 and 186 nM against 3D7 and between 9 and 65 nM and 24 and 359 nM against the K1 strain of P. falciparum. Whereas the IC50 and IC90 values of compounds which exhibited in vivo suppressive activity in mice ranged between 10 and 307 nm and 61 and >965 nM, respectively, against 3D7 and 75 and >806 nm and 241 and >1232 nM against the K1 strain of P. falciparum. The findings suggest that IC90 values against both 3D7 and K1 strains (p < 0.02) are the main contributors for the prediction of in vivo curative activity of a new molecule. Apart from this, a reasonable correlation between MIC and IC50 values of compounds has also been established.

Physical functioning and risk for sleep disorders in US adults: results from the National Health and Nutrition Examination Survey 2005-2014.

OBJECTIVES: Sleep disorders (SDs), particularly problems with falling asleep or daytime sleepiness, have negative impact on health and longevity. Sleep deprivation is also associated with a decline in physical functioning (PF) that mediates the ability to perform activities of daily living. But it remains unknown if deterioration in PF can predict the risk of having a SD. Therefore, the purpose of the present study is to assess the risk of SD associated with PF status in the US adult population. STUDY DESIGN: Cross-sectional study design with data from the National Health and Nutrition Examination Survey from year 2005 to year 2014. METHODS: PF limitation is assessed by reported difficulty in performing 10 tasks selected from PF questionnaire. SD is identified by subjective description of presence of doctor diagnosed SD. Also, five categories of comorbidities that caused difficulty in carrying out these tasks were created. RESULTS: The adults with self-reported PF limitation have 41% higher odds of having a SD (odds ratio [OR] = 1.41, 95% confidence interval [CI] = 1.22-1.59). Moreover, participants having cognitive problems and cardiovascular and pulmonary disorders as secondary conditions that cause difficulty in PF have 145% and 28% higher odds (OR = 2.45 and 1.28; 95% CI = 2.01-3.01 and 1.08-1.53, respectively) of having a SD. Also, females have a 27% lower odds of having a SD than males (OR = 0.73, 95% CI = 0.63-0.83). CONCLUSION: Risk for SD is associated with increasing level of functional disability. We advocate the importance of engagement in physical activities to prevent or delay the onset of SD.

Immunoprotective effect of lentinan in combination with miltefosine on Leishmania-infected J-774A.1 macrophages.

Rejuvenation of deteriorated host immune functions is imperative for successful annihilation of Leishmania parasites. The use of immunomodulatory agents may have several advantages as they conquer immunosuppression and, when given in combination, improve current therapeutic regimens. We herein investigated the immunostimulatory potency of a ß-glucan, lentinan either alone or in combination with short dose of standard drug, miltefosine on Leishmania-infected J-774A.1 macrophages. Our study shows that infected macrophages when stimulated with 2.5 µg/mL and above concentrations of lentinan secreted significant amount of host-protective molecules. The in vitro interaction between lentinan and miltefosine showed some synergy (mean sum of fractional inhibitory concentration [mean ∑FIC] 0.87) at IC50 level. Lentinan (2.5 µg/mL) plus low-dose miltefosine (2 µM) displayed heightened level of pro-inflammatory cytokines, IL-12 (13.6-fold) and TNF-α (6.8-fold) along with nitric oxide (7.2-fold higher) when compared with infected control. In combination group, we also observed remarkably (P<.001) suppressed levels of anti-inflammatory cytokines, IL-10 and TGF-ß, than that of untreated macrophages. Additionally, in comparison with infected group, we observed significant induction in phagocytic activity of macrophages in combination with treated group. Collectively, these findings emphasize the immunostimulatory effect of lentinan alone and in combination with low dose of miltefosine against Leishmania donovani.

Arteether resistance reversal by ketoconazole/fluconazole in rodent malaria parasite Plasmodium vinckei.

Artemisinin and its derivative arteether (ART) are fast acting antimalarial drugs against chloroquine-resistant. There are several partner drugs that are identified as a potential drug for artemisinin combination therapy (ACT) to develop as the antimalarial drug. Limited studies have been carried out in ART drug combination that may have more promising as ACT for resistant Plasmodium parasite. Here, we are the first to show the ART drug resistance reversal in Plasmodium vinckei by using antifungal azole compounds ketoconazole (KTZ) and fluconazole (FCZ). Our previous study has shown that higher antioxidant enzyme, glutathione, and less hemozoin may be correlated with ART resistance in P. vinckei (PvAR). We further hypothesized that glutathione and heme catabolism may be interfered by KTZ and FCZ, resulting in an increased efficacy of ART in PvAR parasite. The results of present study demonstrate synergetic effect of KTZ and FCZ against PvAR parasite, since none of the mice developed infection up to day 10 after combination with ART. These results further showed that ED90 of ART was reduced from 17.23 to 2.19 and 2.56 mg/kg when used in combination with KTZ and FCZ, respectively. Resultant, activity enhancement index (AEI) of ART is significantly increased to 8.60 and 6.73 with partner agents. These studies propose the possibility of ART drug combination that may be helpful in prolonging the life of drug and a promising lead to reduce the chance of resistance development of artemisinin and its derivative.

Is Quadriceps-Strengthening Exercises (QSE) in Medial-Compartment Knee Osteoarthritis with Neutral and Varus Malalignment a Paradox? - A Risk-Appraisal of Strength-Training on Disease Progression.

Introduction: The present inquiry seeks to investigate whether the current regimens of QSEs (Quadriceps-Strengthening Exercises) aggravate the disease while mitigating symptoms. Materials and methods: A comparative study was conducted on 32 patients with medial compartment osteoarthritis of knees. While the neutral group of 16 patients was constituted of those with an anatomical-lateral-femoro-tibial-angle (aFTA) 176-180º, varus group comprised an equal number of patients with an aFTA >180º. A home-based 12-week strength-training program involving weekly visits to hospital for supervised sessions was administered. The outcome measures were visual-analog-scale (VAS), medial patello-femoral joint tenderness (MPFJT), time-up-and-go-test (TUGT), stair-climb test, step test, WOMAC, IKDC scores, aFTA, hip-knee-ankle (HKA) angle, lateral-tibio-femoral-joint-separation (LTFJS), and horizontal-distance-from-centre-of-knee-to-Mikulicz-line. Results: There was a significant increase in quadriceps strength (p<0.01) in both groups. Values for neutral group with VAS score (p=0.01), MPFJT (p=0.01), TUGT (p=0.01), timing of the stair climb test (p=0.01), WOMAC (p<0.01), and IKDC (p=0.03) were better compared to varus group with VAS score (p=0.13), MPFJT (p=0.03), TUGT (p=0.90), timing of stair climb test (p=0.68), WOMAC (p<0.02), and IKDC (p=0.05). Varus group also showed an increase in aFTA and LTFJS in 12 patients, increase in HKA in 11, and increase in horizontal distance from the centre of knee to the Mikulicz line in 7 patients. Conclusion: The present study brings to the fore the paradoxical role played by QSEs in management of medial knee OA. While there is a radiological progression of the disease in both neutral and varus mal-aligned knees more so in the latter than the former.

A natural product inspired hybrid approach towards the synthesis of novel pentamidine based scaffolds as potential anti-parasitic agents.

A natural product inspired molecular hybridization approach led us to a series of novel pentamidine based pyrimidine and chalcone scaffolds. All the hybrids were evaluated for their anti-leishmanial potential. Most of the screened compounds have showed significant in vitro anti-leishmanial activity with less cytotoxicity in comparison to the standard drugs (pentamidine, sodium stibogluconate, and miltefosine). Additionally, anti-malarial screening of these compounds was also done and four compounds have shown superior activity against chloroquine resistance strain (K1) of Plasmodium falciparum.

Prophylactic effect of coconut water (Cocos nucifera L.) on ethylene glycol induced nephrocalcinosis in male wistar rat.

PURPOSE: Many medicinal plants have been employed during ages to treat urinary stones though the rationale behind their use is not well established. Thus, the present study was proposed to evaluate the effect of coconut water as a prophylactic agent in experimentally induced nephrolithiasis in a rat model. MATERIALS AND METHODS: The male Wistar rats were divided randomly into three groups. Animals of group I (control) were fed standard rat diet. In group II, the animals were administrated 0.75% ethylene glycol in drinking water for the induction of nephrolithiasis. Group III animals were administrated coconut water in addition to ethylene glycol. All the treatments were continued for a total duration of seven weeks. RESULTS AND CONCLUSION: Treatment with coconut water inhibited crystal deposition in renal tissue as well as reduced the number of crystals in urine. Furthermore, coconut water also protected against impaired renal function and development of oxidative stress in the kidneys. The results indicate that coconut water could be a potential candidate for phytotherapy against urolithiasis.

Amino Acid Tracer PET MRI in Glioma Management: What a Neuroradiologist Needs to Know.

PET with amino acid tracers provides additional insight beyond MR imaging into the biology of gliomas that can be used for initial diagnosis, delineation of tumor margins, planning of surgical and radiation therapy, assessment of residual tumor, and evaluation of posttreatment response. Hybrid PET MR imaging allows the simultaneous acquisition of various PET and MR imaging parameters in a single investigation with reduced scanning time and improved anatomic localization. This review aimed to provide neuroradiologists with a concise overview of the various amino acid tracers and a practical understanding of the clinical applications of amino acid PET MR imaging in glioma management. Future perspectives in newer advances, novel radiotracers, radiomics, and cost-effectiveness are also outlined.

Coumarin-trioxane hybrids: synthesis and evaluation as a new class of antimalarial scaffolds.

First synthesis of novel coumarin-trioxane hybrids is reported. The synthesis was achieved via condensation of ß-hydroxyhydroperoxides with coumarinic-aldehydes in presence of p-toluenesulfonic acid in good yields and the novel hybrids were evaluated for their antimalarial activity both in vitro and in vivo.

Self retentive partial silicone auricular prosthesis: a case report.

An auricular prosthesis may be required for a number of conditions including congenital abnormalities, malignancy and trauma, which result in disfigurement of the pinna. Whatever the cause of the absence of the pinna, it is a significant loss of a prominent part of the face for the person involved. This article describes a simple and cost effective technique for retention of a silicone partial auricular prosthesis. A Fish-bone shaped substructure (FSS) designed and fabricated using orthodontic wire and autopolymerizing acrylic resin, was embedded into the silicone elastomer of a self-retentive silicone prosthesis. The prosthesis is designed to overcome the disadvantages associated with traditionally fabricated prostheses; namely poor structural strength, inadequate retention, poor adaptation and durability over time.

Effect of precursors feeding and media manipulation on production of novel anticancer pro-drug camptothecin from endophytic fungus.

We have established methodology for the isolation and characterization of a novel endophytic fungus from the inner bark of medicinal plant Nothapodytes foetida, which produced camptothecin in Sabouraud broth (SB) under shake flask conditions. Camptothecin and its related compounds are at present obtained by extraction from intact plants, but fungal endopytes may be an alternative source of production. In present study we have observed the effect of different nutrient combinations and precursors (tryptophan, tryptamine, geraniol, citral, mevalonic acid and leucine) on the accumulation of camptothecin by endophytic fungus Entrophospora infrequens. The precursors were fed either alone or in combinations (tryptophan and geraniol, tryptophan and citral, tryptophan and mevalonic acid, tryptophan and leucine). The highest camptothecin content was observed in the range of 503 ± 25µg/100g dry cell mass in Sabouraud medium. Camptothecin content in the medium was increased by 2.5 folds by the presence of tryptophan and leucine whereas the production with trytophan was also significantly different from other treatments. Furthermore, the effect of fungal camptothecin on the morphology of human cancer cell lines was also studied. The treated cells showed reduction in size, condensation of nucleus and the protoplasmic extensions were reduced. All these characteristics are found in apoptotic cells.

Peri-operative management of a child with ROHHAD-NET syndrome undergoing neural crest tumour excision.

A nine-year-old girl diagnosed with ROHHAD-NET (rapid-onset obesity, hypothalamic dysfunction, hypoventilation, autonomic dysfunction and neuroendocrine tumour) syndrome was scheduled for excision of a large paravertebral ganglioneuroma under general anaesthesia. Her comorbidities included hypothyroidism, diabetes insipidus and autonomic dysfunction. Intra- and postoperative complications included intra-operative hypotension, long surgical time and prolonged postoperative ventilation. Complete weaning from ventilation was initially unsuccessful and she was ultimately discharged on domiciliary nasal BiPAP therapy. The peri-operative care of children with this syndrome is challenging due to the involvement of multiple organ systems. In this report, we describe how pre-operative optimisation, well-planned intra-operative management and intensive postoperative care are essential for a favourable outcome.

Adding MR Diffusion Imaging and T2 Signal Intensity to Neck Imaging Reporting and Data System Categories 2 and 3 in Primary Sites of Postsurgical Oral Cavity Carcinoma Provides Incremental Diagnostic Value.

BACKGROUND AND PURPOSE: The NI-RADS lexicon doesn't use ADC parameters and T2 weighted signal for ascribing categories. We explored ADC, DWI, and T2WI to examine the diagnostic accuracy in primary sites of postsurgical oral cavity carcinoma in the Neck Imaging Reporting and Data System (NI-RADS) categories 2 and 3. MATERIALS AND METHODS: We performed a retrospective analysis in clinically asymptomatic post-surgically treated patients with oral cavity squamous cell carcinoma who underwent contrast-enhanced MRI between January 2013 and January 2016. Histopathology and follow-up imaging were used to ascertain the presence or absence of malignancy in subjects with "new enhancing lesions," which were interpreted according to the NI-RADS lexicon by experienced readers, including NI-RADS 2 and 3 lesions in the primary site. NI-RADS that included T2WI and DWI (referred to as NI-RADS A) and ADC (using the best cutoff from receiver operating characteristic curve analysis, NI-RADS B) was documented in an Excel sheet to up- or downgrade existing classic American College of Radiology NI-RADS and calculate diagnostic accuracy. RESULTS: Sixty-one malignant and 23 benign lesions included in the study were assigned American College of Radiology NI-RADS 2 (n = 33) and NI-RADS 3 (n = 51) categories. The recurrence rate was 90% (46/51) for NI-RADS three, 45% (15/33) for NI-RADS 2, and 73% (61/84) overall. T2WI signal morphology was intermediate in 45 subjects (53.5%) and restricted DWI in 54 (64.2%). Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the American College of Radiology NI-RADS were the following: NI-RADS (75.4%, 78.3%, 90.1%, 54.5%, and 76.1%); NI-RADS A (79.1%, 81.2%, 91.9%, 59.1%, and 79.6%); and NI-RADS B (88.9%, 72.7%, 91.4%, 66.7%, and 85.1%), respectively. CONCLUSIONS: Adding MR imaging diagnostic characteristics like T2WI, DWI, and ADC to the American College of Radiology NI-RADS improved diagnostic accuracy and sensitivity.

In vitro activities of new 2-substituted quinolines against Leishmania donovani.

A series of 9 quinolines and 18 styrylquinolines was evaluated for the drugs' in vitro antileishmanial activities and cytotoxicities. The 7-aroylstyrylquinoline scaffold appeared to be the most promising one, with the most interesting compound, no. 35, exhibiting a 50% inhibitory concentration (IC(50)) of 1.2 µM and a selectivity index value of 121.5. Compound 35 was 10-fold and 8-fold more active than miltefosine and sitamaquine, the reference compounds, with selectivity indexes 607-fold and 60-fold higher, respectively.