Experimental Realization of Nonunitary Multiqubit Operations.

We demonstrate a novel experimental tool set that enables irreversible multiqubit operations on a quantum platform. To exemplify our approach, we realize two elementary nonunitary operations: the or and nor gates. The electronic states of two trapped ^{40}Ca^{+} ions encode the logical information, and a cotrapped ^{88}Sr^{+} ion provides the irreversibility of the gate by a dissipation channel through sideband cooling. We measure 87% and 81% success rates for the or and nor gates, respectively. The presented methods are a stepping stone toward other nonunitary operations such as in quantum error correction and quantum machine learning.

Phonon Laser in the Quantum Regime.

We demonstrate a trapped-ion system with two competing dissipation channels, implemented independently on two ion species cotrapped in a Paul trap. By controlling coherent spin-oscillator couplings and optical pumping rates we explore the phase diagram of this system, which exhibits a regime analogous to that of a (phonon) laser but operates close to the quantum ground state with an average phonon number of n[over ¯]<10. We demonstrate phase locking of the oscillator to an additional resonant drive, and also observe the phase diffusion of the resulting state under dissipation by reconstructing the quantum state from a measurement of the characteristic function.

Generation of a Maximally Entangled State Using Collective Optical Pumping.

We propose and implement a novel scheme for dissipatively pumping two qubits into a singlet Bell state. The method relies on a process of collective optical pumping to an excited level, to which all states apart from the singlet are coupled. We apply the method to deterministically entangle two trapped ^{40}Ca^{+} ions. Within 16 pumping cycles, an initially separable state is transformed into one with 83(1)% singlet fidelity, and states with initial fidelity of ⪆70% converge onto a fidelity of 93(1)%. We theoretically analyze the performance and error susceptibility of the scheme and find it to be insensitive to a large class of experimentally relevant noise sources.

The mechanisms of sorafenib resistance in hepatocellular carcinoma: theoretical basis and therapeutic aspects.

Sorafenib is a multikinase inhibitor capable of facilitating apoptosis, mitigating angiogenesis and suppressing tumor cell proliferation. In late-stage hepatocellular carcinoma (HCC), sorafenib is currently an effective first-line therapy. Unfortunately, the development of drug resistance to sorafenib is becoming increasingly common. This study aims to identify factors contributing to resistance and ways to mitigate resistance. Recent studies have shown that epigenetics, transport processes, regulated cell death, and the tumor microenvironment are involved in the development of sorafenib resistance in HCC and subsequent HCC progression. This study summarizes discoveries achieved recently in terms of the principles of sorafenib resistance and outlines approaches suitable for improving therapeutic outcomes for HCC patients.

Dissipative quantum error correction and application to quantum sensing with trapped ions.

Quantum-enhanced measurements hold the promise to improve high-precision sensing ranging from the definition of time standards to the determination of fundamental constants of nature. However, quantum sensors lose their sensitivity in the presence of noise. To protect them, the use of quantum error-correcting codes has been proposed. Trapped ions are an excellent technological platform for both quantum sensing and quantum error correction. Here we present a quantum error correction scheme that harnesses dissipation to stabilize a trapped-ion qubit. In our approach, always-on couplings to an engineered environment protect the qubit against spin-flips or phase-flips. Our dissipative error correction scheme operates in a continuous manner without the need to perform measurements or feedback operations. We show that the resulting enhanced coherence time translates into a significantly enhanced precision for quantum measurements. Our work constitutes a stepping stone towards the paradigm of self-correcting quantum information processing.

Preparation of Entangled States through Hilbert Space Engineering.

We apply laser fields to trapped atomic ions to constrain the quantum dynamics from a simultaneously applied global microwave field to an initial product state and a target entangled state. This approach comes under what has become known in the literature as "quantum Zeno dynamics" and we use it to prepare entangled states of two and three ions. With two trapped ^{9}Be^{+} ions, we obtain Bell state fidelities up to 0.990_{-5}^{+2}; with three ions, a W-state fidelity of 0.910_{-7}^{+4} is obtained. Compared to other methods of producing entanglement in trapped ions, this procedure can be relatively insensitive to certain imperfections such as fluctuations in laser intensity.

Dissipative production of a maximally entangled steady state of two quantum bits.

Entangled states are a key resource in fundamental quantum physics, quantum cryptography and quantum computation. Introduction of controlled unitary processes--quantum gates--to a quantum system has so far been the most widely used method to create entanglement deterministically. These processes require high-fidelity state preparation and minimization of the decoherence that inevitably arises from coupling between the system and the environment, and imperfect control of the system parameters. Here we combine unitary processes with engineered dissipation to deterministically produce and stabilize an approximate Bell state of two trapped-ion quantum bits (qubits), independent of their initial states. Compared with previous studies that involved dissipative entanglement of atomic ensembles or the application of sequences of multiple time-dependent gates to trapped ions, we implement our combined process using trapped-ion qubits in a continuous time-independent fashion (analogous to optical pumping of atomic states). By continuously driving the system towards the steady state, entanglement is stabilized even in the presence of experimental noise and decoherence. Our demonstration of an entangled steady state of two qubits represents a step towards dissipative state engineering, dissipative quantum computation and dissipative phase transitions. Following this approach, engineered coupling to the environment may be applied to a broad range of experimental systems to achieve desired quantum dynamics or steady states. Indeed, concurrently with this work, an entangled steady state of two superconducting qubits was demonstrated using dissipation.

Small- and wide-angle X-ray scattering (SWAXS) for quantification of aspirin content in a binary powder mixture.

This article presents a novel application of small and wide angle X-ray scattering (SWAXS) in the assessment of aspirin and lactose content in a binary pharmaceutical powder formulation. It is shown that the content correlates with the intensity of the SAXS signal and the intensity of polymorph fingerprints in the WAXS spectra that are collected from the same samples. Because the polymorph WAXS fingerprints and the SAXS signal are two independent characteristics of the same sample, simultaneous SWAXS analysis provides the basis for a dual independent assessment of the same contents.

Dissipative preparation of entanglement in optical cavities.

We propose a novel scheme for the preparation of a maximally entangled state of two atoms in an optical cavity. Starting from an arbitrary initial state, a singlet state is prepared as the unique fixed point of a dissipative quantum dynamical process. In our scheme, cavity decay is no longer undesirable, but plays an integral part in the dynamics. As a result, we get a qualitative improvement in the scaling of the fidelity with the cavity parameters. Our analysis indicates that dissipative state preparation is more than just a new conceptual approach, but can allow for significant improvement as compared to preparation protocols based on coherent unitary dynamics.

Route to attosecond nonlinear spectroscopy.

We demonstrate generation of coherent microjoule-scale, low-order harmonic supercontinua in the deep and vacuum ultraviolet (4-9 eV), resulting from the nonlinear transformations of near-single-cycle laser pulses in a gas cell. We show theoretically that their formation is connected to a novel nonlinear regime, holding promise for the generation of powerful deep-UV and vacuum ultraviolet subfemtosecond pulses. Our work opens the route to pump-probe spectroscopy of subfemtosecond-scale valence-shell phenomena in atoms, molecules, and condensed matter.

WS5, a direct target of oncogenic transcription factor Myc, is related to human melanoma glycoprotein genes and has oncogenic potential.

We have isolated a gene (WS5) that is specifically expressed at the mRNA and protein level in avian fibroblasts transformed by the v-myc oncogene of avian acute leukemia virus MC29. In a conditional cell transformation system, WS5 gene expression was tightly correlated with v-myc activation. The WS5 gene contains 11 exons, encoding a 733-amino acid protein with a transmembrane region and a polycystic kidney disease (PKD) domain. Near the transcriptional start site, the WS5 promoter contains a cluster of four binding sites for the Myc-Max complex and a binding site for transcription factor C/EBPalpha. Electrophoretic mobility shift assays and chromatin immunoprecipitation showed that Myc, Max and C/EBPalpha bind specifically to these sites. Functional promoter analyses revealed that both the Myc-binding site cluster and the C/EBPalpha-binding site are essential for strong transcriptional activation, and that Myc and C/EBPalpha synergistically activate the WS5 promoter. Ectopic expression of WS5 led to cell transformation documented by anchorage-independent growth. The human melanoma antigen Pmel17, a type I transmembrane glycoprotein, is the mammalian protein with the highest amino acid sequence identity (38%) to WS5. The Pmel17 gene is regulated by the MITF protein, a bHLHZip transcription factor with DNA binding specificities similar to those of Myc/Max. WS5 is also related to human glycoprotein GPNMB expressed in metastatic melanoma cells and implicated in the progression of brain and liver tumors.

[Food allergy in the child: an exploratory study on the impact of the elimination diet on food neophobia]. / Impact du régime d'éviction sur la néophobie dans le cadre d'une allergie alimentaire chez l'enfant : étude exploratoire.

OBJECTIVES: This study was designed to analyse the impact of an elimination diet in children with food allergy, and its perception by their parents on the later reticence of children to test unknown foods, food neophobia. METHODS: The degree of food neophobia of children having outgrown their allergy (mean age, 7 years 2 months) was compared to that of a sibling (9 years 5 months) using a standardized scale and a questionnaire of food friendliness. Parents were also asked to fill in a questionnaire on the disease and its burden on the family. RESULTS: Children having outgrown their allergy are more reluctant to test new foods than their non-allergic brother or sister, as shown by their scoring on the food neophobia scale and the number of unknown foods following the cure of the disease. Two factors increase the level of food neophobia, the distressing effect and the duration of the period elapsed until the diagnosis was made, as well as the distressing effect and the lack of variety in the meal preparation. CONCLUSION: Food neophobia, a normal phase between 2 and 10 years, is worsened by the elimination diet required by food allergy, especially in case of late diagnosis and when the time elapsed before diagnosis and the preparation of meals were perceived as difficult to bear.

[Validation of the Hannover Score for Polytrauma Outcome (HASPOC) in a sample of 170 polytrauma patients and a comparison with the 12-Item Short-Form Health Survey]. / Hannover Score for Polytrauma Outcome (HASPOC). Validierung am Beispiel von 170 Polytrauma-Patienten und Vergleich mit dem SF-12.

Improved survival rates of patients with multiple injuries have increased general interest in the quality of rehabilitation status after polytrauma. Due to the complex nature of multiple injuries, a special score is needed to evaluate the outcome after polytrauma. The aim of this study was to validate the Hannover Score for Polytrauma Outcome (HASPOC). One hundred seventy patients who had sustained multiple injuries were re-examined using the HASPOC 2 years after trauma. Results were correlated with the 12-Item Short Form Health Survey (SF-12), a validated and established scoring system. The HASPOC was also correlated with clinical parameters predictive of poor outcome. Two control groups consisting of either patients after single injuries or healthy controls were also evaluated using the HASPOC. In the group of patients after multiple injuries, the HASPOC correlated with the SF-12 in injury severity and polytrauma scores, intubation period, hospital stay, and occurrence of injuries below the knee. Differences between healthy controls,patients after single injuries, and patients after multiple injuries were statistically significant when evaluated with the HASPOC. This statistical significance was not achieved using the SF-12. The HASPOC is a valid scoring system and useful for evaluating the rehabilitation status after polytrauma.

JAC, a direct target of oncogenic transcription factor Jun, is involved in cell transformation and tumorigenesis.

Using subtractive hybridization techniques, we have isolated a gene termed JAC that is strongly and specifically activated in avian fibroblasts transformed by the v-jun oncogene of avian sarcoma virus 17 (ASV17), but not in cells transformed by other oncogenic agents. Furthermore, JAC is highly expressed in cell lines derived from jun-induced avian fibrosarcomas. Kinetic analysis using a doxycycline-controlled conditional cell transformation system showed that expression of the 0.8-kb JAC mRNA is induced rapidly upon activation of the oncogenic v-jun allele. Nucleotide sequence analysis and transcriptional mapping revealed that the JAC gene contains two exons, with the longest ORF confined to exon 2. The deduced 68-amino acid chicken JAC protein is rich in cysteine residues and displays 37% sequence identity to mammalian high-sulfur keratin-associated proteins. The promoter region of JAC contains a consensus (5'-TGACTCA-3') and a nonconsensus (5'-TGAGTAA-3') AP-1 binding site in tandem, which are both specifically bound by the Gag-Jun hybrid protein encoded by ASV17. Mutational analysis revealed that the two AP-1 sites confer strong transcriptional activation by Gag-Jun in a synergistic manner. Ectopic expression of JAC in avian fibroblasts leads to anchorage-independent growth, strongly suggesting that deregulation of JAC is an essential event in jun-induced cell transformation and tumorigenesis.

Post-stroke spasticity management with repeated botulinum toxin injections in the upper limb.

OBJECTIVE: Although the botulinum toxin A (BTX-A) treatment has proved effective in spasticity management, no information is available with regard to the effects of repeated injections over time. DESIGN: To evaluate the effects of BTX-A on moderate or severe upper limb spasticity, an exploratory investigation was performed on 28 stroke patients treated for 2 yr or longer and observed for 3 yr. Every 3 to 5 mo, each patient received BTX-A injections in upper limb muscles. The assessment, performed before and 1 mo after each injection for a median of 28 mo, included technical and functional objectives and the burden of care. The former were evaluated by using the modified Ashworth Scale for spasticity and the goniometric measurement of rest position and range of motion; functional objectives were evaluated by means of the Frenchay Arm Test and a patient/caregiver goals assessment scale. RESULTS: BTX-A treatment was followed by an improvement in all technical outcome measures. Motor dexterity scores improved in only 8 of 28 patients, vs. daily living activities, which increased in all subjects. Although the average dosage injected per session did not change, intervals between injections became longer. No relationship between either spasticity onset or residual motoricity and response to treatment could be found. CONCLUSIONS: This investigation is relevant clinically because repeated BTX-A injections show unchanging effectiveness in the management of focal spasticity after stroke.

Botulinum toxin type A and short-term electrical stimulation in the treatment of upper limb flexor spasticity after stroke: a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To investigate whether the combined approach of botulinum toxin type A (BtxA) and electrical stimulation was more effective than the toxin alone in the treatment of chronic upper limb spasticity after stroke. DESIGN: Randomized, placebo-controlled study with four treatment groups: 1000 units BtxA (Dysport) + electrical stimulation (A), 1000 units BtxA (B), placebo + electrical stimulation (C) and placebo (D). SETTING: A neurological rehabilitation clinic. SUBJECTS: Twenty-four stroke patients with chronic upper limb spasticity after stroke, six patients in each treatment group. INTERVENTIONS: Intramuscular injection of either toxin or placebo into six upper imb flexor muscles. In group A and C additional electrical stimulation of the injected muscles with surface electrodes, three times half an hour each day for three days. MAIN OUTCOME MEASURES: Muscle tone rated with the modified Ashworth score, limb position at rest and difficulties encountered during three upper limb motor tasks assessed before and 2, 6 and 12 weeks after injection. RESULTS: Most improvements were observed in patients of group A. Cleaning the palm (p = 0.004) differed across groups. Pairwise comparison for this target variable showed that group A differed from group B and D (p <0.01), but not from C. Indicative across-group differences were obtained for elbow spasticity reduction (p = 0.011), and improvement of putting the arm through a sleeve (p = 0.020). CONCLUSIONS: The placebo-controlled trial favours the concept that electrical stimulation enhances the effectiveness of BtxA in the treatment of chronic upper limb flexor spasticity after stroke.

Low-dose botulinum toxin with ankle taping for the treatment of spastic equinovarus foot after stroke.

OBJECTIVE: To evaluate the efficacy of a combined treatment for spastic foot using selective injections of botulinum toxin (BTA) into the tibialis posterior muscle followed by ankle taping, and to compare it with current BTA treatment procedure. DESIGN: Single-blind randomized control trial. Three-month follow-up after treatment. SETTING: Neurorehabilitation clinic. SUBJECTS: Eighteen outpatients with equinovarus foot due to severe spasticity after stroke. INTERVENTIONS: (1) Injection of 190 to 320 BTA U into several calf muscles (group A); (2) injection of 100 BTA U into the tibialis posterior muscle, followed by ankle-foot taping (group B). MAIN OUTCOME MEASURES: Ankle range of motion (ROM), Ashworth scale, gait velocity, and step length. RESULTS: Average Ashworth scores decreased 1 point in both groups, but the benefit appeared of shorter duration in group B. Changes in both foot position at rest and passive ankle ROM were observed in all patients, without treatment-related differences, except for gain in passive dorsiflexion that appeared higher in group A. Gait velocity and step length showed similar increases in both groups. CONCLUSION: The combination of selective injections of low BTA doses with ankle-foot taping is as effective as the injection of the current doses for the reduction of foot inversion with positive effects on gait parameters.

Immediate effects of therapeutic facilitation on the gait of hemiparetic patients as compared with walking with and without a cane.

OBJECTIVES: Although the neurodevelopmental technique (Bobath) is the most widely used approach in the gait rehabilitation of hemiparetic subjects in Europe, there is little neurophysiological evidence for its presumed effects on gait symmetry and facilitation of paretic muscles during the therapeutic intervention. The study, therefore, investigated the immediate effects of gait entrainment by a physical therapist on the gait of hemiparetic subjects. METHODS: Cycle parameters, gait symmetry, hip joint movement and the electromyographic activity of several lower limb muscles were assessed in 22 patients during a classic intervention by five Bobath therapists and while walking with and without a cane. RESULTS: Multivariate statistics revealed that, while being assisted by the therapist, patients walked faster (P = 0.022), with a longer relative stance period of the affected leg (P = 0.005), a higher symmetry (P = 0.002), larger hip extension (P = 0.001) and more activation (P = 0.026) of the Mm. triceps surae, vastus lateralis, biceps femoris and gluteus medius as compared to walking with and without a cane. Extensor spasticity of the plantar-flexor tended to increase (n.s.). In five subjects, no after-effect could be documented 1 h after a gait training of 30 min. CONCLUSIONS: The study confirmed a more balanced walking pattern in conjunction with facilitation of various weight bearing muscles during the therapeutic intervention. A prolonged single stance period of the affected leg, an unobstructed hip movement, enhanced weight acceptance and a faster gait seemed to be responsible for the observed immediate effects of the therapeutic intervention.

Asymmetry of gait initiation in hemiparetic stroke subjects.

OBJECTIVE: To investigate symmetry of gait initiation in healthy and hemiparetic subjects. DESIGN: Survey. SETTING: Kinematic laboratory affiliated with a hospital-based department of rehabilitation. PATIENTS OR OTHER PARTICIPANTS: Ten healthy and 14 hemiparetic stroke subjects starting five times with their right and left leg, respectively. MAIN OUTCOME MEASURES: Duration of defined periods, step length, center of pressure, and center of mass were recorded and calculated using two triaxial force plates, contact switches, and a video camera system. RESULTS: Healthy subjects displayed a high degree of independence of kinetic and kinematic parameters of the starting limb. Hemiparetic patients showed differences with respect to the starting limb: when starting with the nonaffected leg, the swing period and step length was shorter and the center of pressure displayed a more marked medio-lateral sway with no corresponding initial movement of the center of mass; when starting with the affected leg the movement pattern of the center of pressure and center of mass was comparable to that of normal subjects. CONCLUSIONS: The trajectories of the center of pressure and center of mass and the symmetry parameters are in accordance with a higher degree of uncertainty when starting with the non-affected limb in hemiparetic subjects.