Identifying medical mimics for late-life mania: A case of prion disease.

Sporadic Creutzfeld Jakob Disease is a rare disease with diagnostic challenges. While there is very little human data regarding this disease, some studies have indicated that certain medications may be useful in slowing its progression. Case study data implies psychiatric and cognitive symptoms preceding the diagnosis. This single case report presents a 68-year-old male with suspected late-onset bipolar disorder, later found to have sporadic Creutzfeld Jakob Disease. The patient was treated with lithium for this purported bipolar disorder. Approximately 2 years later, the patient met the Center for Disease Control (CDC) diagnostic criteria for prion disease following a rapid decline in cognition. This case provides an example of a medical mimic of bipolar disorder in the geriatric population.

Controlling NMR spin systems for quantum computation.

Nuclear magnetic resonance is arguably both the best available quantum technology for implementing simple quantum computing experiments and the worst technology for building large scale quantum computers that has ever been seriously put forward. After a few years of rapid growth, leading to an implementation of Shor's quantum factoring algorithm in a seven-spin system, the field started to reach its natural limits and further progress became challenging. Rather than pursuing more complex algorithms on larger systems, interest has now largely moved into developing techniques for the precise and efficient manipulation of spin states with the aim of developing methods that can be applied in other more scalable technologies and within conventional NMR. However, the user friendliness of NMR implementations means that they remain popular for proof-of-principle demonstrations of simple quantum information protocols.

Posterior Tibial Slope in Patients Undergoing Anterior Cruciate Ligament Reconstruction With Patellar Tendon Autograft: Analysis of Subsequent ACL Graft Tear or Contralateral ACL Tear.

BACKGROUND: Reports on greater posterior tibial slope (PTS) and its relationship to subsequent anterior cruciate ligament (ACL) injury show conflicting results; it has not been studied much in patients after ACL reconstruction with patellar tendon autograft (PTG). HYPOTHESIS: Patients who suffered a subsequent ACL injury would have a larger PTS than patients who did not suffer a subsequent injury after primary or revision ACL reconstruction. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: Patients received primary (n = 2439) or revision (n = 324) ACL reconstruction with PTG and were followed prospectively to determine the rate of graft tear and contralateral ACL tear. The PTS was measured preoperatively on digital lateral view radiographs. Intersecting lines were drawn along the medial tibial plateau and posterior tibia; the value of the acute angle at the lines' intersection was then subtracted from 90° to obtain the PTS. This procedure was completed by a clinical assistant with an intrarater reliability of 0.89. Chi-square analysis and t tests were used to determine the differences between rate of tears and measurements between groups. A threshold of PTS ≥10° was used for analysis. RESULTS: The mean follow-up time was 11.6 ± 4.0 years. After primary surgery, the mean PTS in patients with graft tears was 5.4°± 3.1° versus 4.8°± 2.9° for patients without a tear (P = .041). The mean PTS was 4.9°± 3.4° for patients with contralateral tears (not statistically significantly different than the no-tear group; P = .80). Furthermore, patients with primary reconstruction with PTS ≥10° had a statistically significantly higher rate of graft tear (9.7%) than patients with PTS ≤9° (4.8%) (P = .003), but not a higher rate of contralateral tear. Among patients undergoing revision surgery, there were no statistically significant differences between the graft tear, contralateral tear, and no-tear groups with relation to PTS ≥10°. CONCLUSION: After primary ACL reconstruction, patients with PTS >10° had a higher rate of subsequent graft tear but not a higher rate of contralateral tear. With revision surgery, there was no significant association between PTS and the rate of subsequent tear. Therefore, caution should be exercised when considering more radical interventions, such as osteotomy, to prevent retear in patients with high PTS.

Arbitrary precision composite pulses for NMR quantum computing.

We discuss the implementation of arbitrary precision composite pulses developed using the methods of Brown et al. [K.R. Brown, A.W. Harrow, I.L. Chuang, Arbitrarily accurate composite pulse sequences, Phys. Rev. A 70 (2004) 052318]. We give explicit results for pulse sequences designed to tackle both the simple case of pulse length errors and the more complex case of off-resonance errors. The results are developed in the context of NMR quantum computation, but could be applied more widely.

Quantum correlations which imply causation.

In ordinary, non-relativistic, quantum physics, time enters only as a parameter and not as an observable: a state of a physical system is specified at a given time and then evolved according to the prescribed dynamics. While the state can, and usually does, extend across all space, it is only defined at one instant of time. Here we ask what would happen if we defined the notion of the quantum density matrix for multiple spatial and temporal measurements. We introduce the concept of a pseudo-density matrix (PDM) which treats space and time indiscriminately. This matrix in general fails to be positive for measurement events which do not occur simultaneously, motivating us to define a measure of causality that discriminates between spatial and temporal correlations. Important properties of this measure, such as monotonicity under local operations, are proved. Two qubit NMR experiments are presented that illustrate how a temporal pseudo-density matrix approaches a genuinely allowed density matrix as the amount of decoherence is increased between two consecutive measurements.

Further analysis of some symmetric and antisymmetric composite pulses for tackling pulse strength errors.

Composite pulses have found widespread use in both conventional Nuclear Magnetic Resonance experiments and in experimental quantum information processing to reduce the effects of systematic errors. Here we describe several families of time symmetric and antisymmetric fully compensating composite pulses, inspired by the previous Fn, Gn and BB1 families family developed by Wimperis. We describe families of composite 180° pulses (not gates) which exhibit unprecedented tolerance of pulse strength errors without unreasonable sensitivity to off-resonance errors, and related families with more exotic tailored responses. Next we address the problem of extending these methods to other rotation angles, and discuss numerical results for 90° pulses. Finally we demonstrate the performance of some 90° and 180° pulses in NMR experiments.

Implementing quantum logic gates with gradient ascent pulse engineering: principles and practicalities.

We briefly describe the use of gradient ascent pulse engineering (GRAPE) pulses to implement quantum logic gates in nuclear magnetic resonance quantum computers, and discuss a range of simple extensions to the core technique. We then consider a range of difficulties that can arise in practical implementations of GRAPE sequences, reflecting non-idealities in the experimental systems used.

Group epitope mapping considering relaxation of the ligand (GEM-CRL): including longitudinal relaxation rates in the analysis of saturation transfer difference (STD) experiments.

In the application of saturation transfer difference (STD) experiments to the study of protein-ligand interactions, the relaxation of the ligand is one of the major influences on the experimentally observed STD factors, making interpretation of these difficult when attempting to define a group epitope map (GEM). In this paper, we describe a simplification of the relaxation matrix that may be applied under specified experimental conditions, which results in a simplified equation reflecting the directly transferred magnetisation rate from the protein onto the ligand, defined as the summation over the whole protein of the protein-ligand cross-relaxation multiplied by with the fractional saturation of the protein protons. In this, the relaxation of the ligand is accounted for implicitly by inclusion of the experimentally determined longitudinal relaxation rates. The conditions under which this "group epitope mapping considering relaxation of the ligand" (GEM-CRL) can be applied were tested on a theoretical model system, which demonstrated only minor deviations from that predicted by the full relaxation matrix calculations (CORCEMA-ST) [7]. Furthermore, CORCEMA-ST calculations of two protein-saccharide complexes (Jacalin and TreR) with known crystal structures were performed and compared with experimental GEM-CRL data. It could be shown that the GEM-CRL methodology is superior to the classical group epitope mapping approach currently used for defining ligand-protein proximities. GEM-CRL is also useful for the interpretation of CORCEMA-ST results, because the transferred magnetisation rate provides an additional parameter for the comparison between measured and calculated values. The independence of this parameter from the above mentioned factors can thereby enhance the value of CORCEMA-ST calculations.

Magnetic field sensing beyond the standard quantum limit using 10-spin NOON states.

Quantum entangled states can be very delicate and easily perturbed by their external environment. This sensitivity can be harnessed in measurement technology to create a quantum sensor with a capability of outperforming conventional devices at a fundamental level. We compared the magnetic field sensitivity of a classical (unentangled) system with that of a 10-qubit entangled state, realized by nuclei in a highly symmetric molecule. We observed a 9.4-fold quantum enhancement in the sensitivity to an applied field for the entangled system and show that this spin-based approach can scale favorably as compared with approaches in which qubit loss is prevalent. This result demonstrates a method for practical quantum field sensing technology.

Quantum information processing with delocalized qubits under global control.

Conventional quantum computing schemes are incompatible with nanometer-scale "hardware," where the closely packed spins cannot be individually controlled. We report the first experimental demonstration of a global control paradigm: logical qubits delocalize along a spin chain and are addressed via the two terminal spins. Using NMR studies on a three-spin molecule, we implement a globally clocked quantum mirror that outperforms the equivalent swap network. We then extend the protocol to support dense qubit storage and demonstrate this experimentally via Deutsch and Deutsch-Jozsa algorithms.

Contrasting photochemical and thermal reactivity of Ru(CO)2(PPh3)(dppe) towards hydrogen rationalised by parahydrogen NMR and DFT studies.

The synthesis, characterisation and thermal and photochemical reactivity of Ru(CO)2(PPh3)(dppe) 1 towards hydrogen are described. Compound proved to exist in both fac (major) and mer forms in solution. Under thermal conditions, PPh3 is lost from 1 in the major reaction pathway and the known complex Ru(CO)2(dppe)(H)2 2 is formed. Photochemically, CO loss is the dominant process, leading to the alternative dihydride Ru(CO)(PPh3)(dppe)(H)2 3. The major isomer of 3, viz. 3a, contains hydride ligands that are trans to CO and trans to one of the phosphorus atoms of the dppe ligand but a second isomer, 3b, where both hydride ligands are trans to distinct phosphines, is also formed. On the NMR timescale, no interconversion of 3a and 3b was observed, although hydride site interchange is evident with activation parameters of DeltaH(double dagger) = 95 +/- 6 kJ mol(-1) and DeltaS(double dagger) = 26 +/- 17 J K(-1) mol(-1). Density functional theory confirms that the observed species are the most stable isomeric forms, and suggests that hydride exchange occurs via a transition state featuring an eta2-coordinated H2 unit.

Robust quantum information processing with techniques from liquid-state NMR.

While nuclear-magnetic-resonance (NMR) techniques are unlikely to lead to a large-scale quantum computer, they are well suited to investigating basic phenomena and developing new techniques. Indeed, it is likely that many existing NMR techniques will find uses in quantum information processing. Here I describe how the composite-rotation (composite-pulse) method can be used to develop quantum logic gates which are robust against systematic errors.

Approximate quantum cloning with nuclear magnetic resonance.

Here we describe a nuclear magnetic resonance (NMR) experiment that uses a three qubit NMR device to implement the one-to-two approximate quantum cloning network of Buzek et al. [Phys. Rev. A 56, 3446 (1997)]. As expected the experimental results indicate that the network clones all input states with similar fidelities, but as a result of decoherence and incoherent evolution arising from B(1) inhomogeneity the total fidelity achieved does not exceed the measurement bound.

Oxidative folding intermediates with nonnative disulfide bridges between adjacent cysteine residues.

The oxidative folding of the Amaranthus alpha-amylase inhibitor, a 32-residue cystine-knot protein with three disulfide bridges, was studied in vitro in terms of the disulfide content of the intermediate species. A nonnative vicinal disulfide bridge between cysteine residues 17 and 18 was found in three of five fully oxidized intermediates. One of these, the most abundant folding intermediate (MFI), was further analyzed by (1)H NMR spectroscopy and photochemically induced dynamic nuclear polarization, which revealed that it has a compact structure comprising slowly interconverting conformations in which some of the amino acid side chains are ordered. NMR pulsed-field gradient diffusion experiments confirmed that its hydrodynamic radius is indistinguishable from that of the native protein. Molecular modeling suggested that the eight-membered ring of the vicinal disulfide bridge in MFI may be located in a loop region very similar to those found in experimentally determined 3D structures of other proteins. We suggest that the structural constraints imposed on the folding intermediates by the nonnative disulfides, including the vicinal bridge, may play a role in directing the folding process by creating a compact fold and bringing the cysteine residues into close proximity, thus facilitating reshuffling to native disulfide bridges.

A combined parahydrogen and theoretical study of H2 activation by 16-electron d8 ruthenium(0) complexes and their subsequent catalytic behaviour.

The photochemical reaction of Ru(CO)(3)(L)(2), where L = PPh(3), PMe(3), PCy(3) and P(p-tolyl)(3) with parahydrogen (p-H(2)) has been studied by in-situ NMR spectroscopy and shown to result in two competing processes. The first of these involves loss of CO and results in the formation of the cis-cis-trans-L isomer of Ru(CO)(2)(L)(2)(H)(2), while in the second, a single photon induces loss of both CO and L and leads to the formation of cis-cis-cis Ru(CO)(2)(L)(2)(H)(2) and Ru(CO)(2)(L)(solvent)(H)(2) where solvent = toluene, THF and pyridine (py). In the case of L = PPh(3), cis-cis-trans-L Ru(CO)(2)(L)(2)(H)(2) is shown to be an effective hydrogenation catalyst with rate limiting phosphine dissociation proceeding at a rate of 2.2 s(-1) in pyridine at 355 K. Theoretical calculations and experimental observations show that H(2) addition to the Ru(CO)(2)(L)(2) proceeds to form cis-cis-trans-L Ru(CO)(2)(L)(2)(H)(2) as the major product via addition over the pi-accepting OC-Ru-CO axis.

Rapid sample-mixing technique for transient NMR and photo-CIDNP spectroscopy: applications to real-time protein folding.

We describe the development and application of a novel rapid sample-mixing technique for real-time NMR (nuclear magnetic resonance) spectroscopy. The apparatus consists of an insert inside a conventional NMR tube coupled to a rapid injection syringe outside the NMR magnet. Efficient and homogeneous mixing of solutions in the NMR tube is achieved with a dead time of tens of milliseconds, without modification of the NMR probe or additional hardware inside the magnet. Provision is made for the inclusion of an optical fiber to allow in situ laser irradiation of samples, for example to generate photo-CIDNP (chemically induced dynamic nuclear polarization). An NMR water suppression method has been implemented to allow experiments in H(2)O as well as in deuterated solvents. The performance of the device has been tested and optimized by a variety of methods, including sensitive detection of residual pH gradients and the use of NMR imaging to monitor the extent of mixing in real time. The potential utility of this device, in conjunction with the sensitivity and selectivity of photo-CIDNP, is demonstrated by experiments on the protein hen lysozyme. These measurements involve the direct detection of spectra during real-time refolding, and the use of CIDNP pulse labeling to study a partially unfolded state of the protein under equilibrium conditions. Magnetization transfer from this disordered state to the well-characterized native state provides evidence for the remarkable persistence of nativelike elements of structure under conditions in which the protein is partially denatured and aggregation prone.

The circularization of amyloid fibrils formed by apolipoprotein C-II.

Amyloid fibrils have historically been characterized by diagnostic dye-binding assays, their fibrillar morphology, and a "cross-beta" x-ray diffraction pattern. Whereas the latter demonstrates that amyloid fibrils have a common beta-sheet core structure, they display a substantial degree of morphological variation. One striking example is the remarkable ability of human apolipoprotein C-II amyloid fibrils to circularize and form closed rings. Here we explore in detail the structure of apoC-II amyloid fibrils using electron microscopy, atomic force microscopy, and x-ray diffraction studies. Our results suggest a model for apoC-II fibrils as ribbons approximately 2.1-nm thick and 13-nm wide with a helical repeat distance of 53 nm +/- 12 nm. We propose that the ribbons are highly flexible with a persistence length of 36 nm. We use these observed biophysical properties to model the apoC-II amyloid fibrils either as wormlike chains or using a random-walk approach, and confirm that the probability of ring formation is critically dependent on the fibril flexibility. More generally, the ability of apoC-II fibrils to form rings also highlights the degree to which the common cross-beta superstructure can, as a function of the protein constituent, give rise to great variation in the physical properties of amyloid fibrils.