A multi-reservoir extruder for time-resolved serial protein crystallography and compound screening at X-ray free-electron lasers.

Serial crystallography at X-ray free-electron lasers (XFELs) permits the determination of radiation-damage free static as well as time-resolved protein structures at room temperature. Efficient sample delivery is a key factor for such experiments. Here, we describe a multi-reservoir, high viscosity extruder as a step towards automation of sample delivery at XFELs. Compared to a standard single extruder, sample exchange time was halved and the workload of users was greatly reduced. In-built temperature control of samples facilitated optimal extrusion and supported sample stability. After commissioning the device with lysozyme crystals, we collected time-resolved data using crystals of a membrane-bound, light-driven sodium pump. Static data were also collected from the soluble protein tubulin that was soaked with a series of small molecule drugs. Using these data, we identify low occupancy (as little as 30%) ligands using a minimal amount of data from a serial crystallography experiment, a result that could be exploited for structure-based drug design.

Implantable vagus nerve stimulation system performance is not affected by internal or external defibrillation shocks.

PURPOSE: Autonomic regulation therapy (ART) for heart failure (HF) is delivered using vagus nerve stimulation (VNS), and has been associated with improvement in cardiac function and HF symptoms. VNS is delivered using an implantable pulse generator (IPG) and a lead placed around the cervical vagus nerve. Because HF patients may receive concomitant cardiac defibrillation therapy, testing was conducted to determine the effect of defibrillation (DF) on VNS system performance. METHODS: Normal swine (n = 4) with VNS system implants on the right cervical vagus nerve received sequential defibrillation shocks with three defibrillation systems: an implantable cardioverter defibrillator (ICD), a subcutaneous ICD (S-ICD), and an external cardioverter defibrillator (ECD). Each system delivered a series of bipolar high-energy shocks and reverse-polarity high-energy shocks. RESULTS: The specified cardiac defibrillation shocks were delivered successfully from each of the three defibrillation systems to all animals. After each shock series, interrogation of the IPG confirmed that software and data were unchanged from pre-programmed values. After all of the defibrillation shocks were delivered, the IPGs underwent and passed comprehensive electrical testing demonstrating proper system function. No shifts in IPG parameters or ART system failures were observed, and histologic evaluation of the vagus nerve revealed no anatomic changes. CONCLUSIONS: Implantable VNS systems were tested in vivo for immunity to defibrillation via ICD, S-ICD, and ECD, and were found to be unaffected by a series of high-energy defibrillation shocks. These results confirm that ART systems are capable of continuing to function after defibrillation and the cervical vagus nerve is anatomically unaffected.

Effect of defibrillation on the performance of an implantable vagus nerve stimulation system.

BACKGROUND: Vagus Nerve Stimulation (VNS) delivers Autonomic Regulation Therapy (ART) for heart failure (HF), and has been associated with improvement in cardiac function and heart failure symptoms. VNS is delivered using an implantable pulse generator (IPG) and lead with electrodes placed around the cervical vagus nerve. Because HF patients may receive concomitant cardiac defibrillation therapy, testing was conducted to determine the effect of defibrillation (DF) on the VNS system. METHODS: DF testing was conducted on three ART IPGs (LivaNova USA, Inc.) according to international standard ISO14708-1, which evaluated whether DF had any permanent effects on the system. Each IPG was connected to a defibrillation pulse generator and subjected to a series of high-energy pulses. RESULTS: The specified series of pulses were successfully delivered to each of the three devices. All three IPGs passed factory electrical tests, and interrogation confirmed that software and data were unchanged from the pre-programmed values. No shifts in parameters or failures were observed. CONCLUSIONS: Implantable VNS systems were tested for immunity to defibrillation, and were found to be unaffected by a series of high-energy defibrillation pulses. These results suggest that this VNS system can be used safely and continue to function after patients have been defibrillated.

Spin polarons in the correlated metallic pyrochlore Cd2Re2O7.

Muon spin rotation spectroscopy reveals localized electron states in the geometrically frustrated metallic pyrochlore Cd2Re2O7 at temperatures from 2 to 300 K in transverse magnetic fields up to 7 T. Two distinctive types of localized states, with characteristic radii of about 0.5 and 0.15 nm, are detected at high and low temperature, respectively. These states may be spin polarons, formed due to strong exchange interaction between itinerant electrons and the magnetic 5d electrons of Re ions, which may determine the peculiar electronic and magnetic properties of Cd2Re2O7.

Electrical Interaction between Implantable Vagus Nerve Stimulation Device and Implantable Cardiac Rhythm Management Device.

BACKGROUND: Autonomic regulation therapy via vagus nerve stimulation (VNS) was recently approved as a therapy for chronic heart failure, and will likely be utilized in patients who are also indicated for cardiac rhythm management device implantation. This study is designed to assess the degree to which VNS is likely to cause interference in the cardiac sensing of an implantable cardiac rhythm management device. METHODS: A VNS stimulation lead and a cardiac sensing lead were placed in a simulated biological medium. A nonconductive carrier frame was used to position the leads at a precise electrode spacing. Stimulation was delivered through the VNS Therapy lead at a maximum output current and a variety of combinations of stimulation frequencies from 5-30 Hz and stimulation pulse widths from 130-1000 µs. The electrode spacing began at 0 cm and was increased in 1 cm increments until the measured signal dropped below the cardiac rhythm management device noise floor for sensing. The test was conducted with both bipolar and unipolar sensing. RESULTS: In the bipolar sensing configuration, the maximum sensed signal amplitude was 687 µV at an electrode separation of 0 cm, signal frequency of 30 Hz, pulse width of 1000 µs, and output current of 3.5 mA. In the unipolar sensing configuration, the maximum amplitude was 406 µV. In both configurations, the measured signal with maximum stimulation intensity decreased significantly with electrode separation, and dropped below the noise floor at an electrode spacing of 3.0 cm. The sensed signal amplitude was further attenuated at lower stimulation amplitudes and pulse widths. CONCLUSION: Even at maximum neural stimulation intensity of 3.5 mA, at an electrode separation of at least 3.0 cm, neural stimulation did not result in a detectable level of interference with either bipolar or unipolar sensing. Because this separation is significantly smaller than the minimum electrode separation of 15 cm in clinical practice, VNS Therapy is not expected to interfere with the function of implantable cardiac devices.

Signatures of new d-wave vortex physics in overdoped Tl2Ba2CuO(6+x) revealed by TF-µ(+)SR.

The spontaneous expulsion of applied magnetic field, the Meissner effect, is a defining feature of superconductors; in Type-II superconductors above the lower critical field, this screening takes the form of a lattice of magnetic flux vortices. Using implanted spin-1/2 positive muons, one can measure the vortex lattice field distribution through the spin precession and deduce key parameters of the superconducting ground state, and thereby fundamental properties of the superconducting pairing. Muon spin rotation/relaxation (µSR) experiments have indeed revealed much interesting physics in the underdoped cuprates, where superconductivity is closely related to, or coexistent with, disordered or fluctuating magnetic and charge excitations. Such complications should be absent in overdoped cuprates, which are believed to exhibit conventional Fermi liquid behaviour. These first transverse field (TF)-µ(+)SR experiments on heavily-overdoped single crystals reveal a superfluid density exhibiting a clear inflection point near 0.5Tc, with a striking doping-independent scaling. This reflects hitherto unrecognized physics intrinsic to d-wave vortices, evidently generic to the cuprates, and may offer fundamentally new insights into their still-mysterious superconductivity.

Complete, superior labral radial tear and type II slap tear associated with greater tuberosity fracture.

This case report presents a unique variant of superior labral-bicep complex injury. The combination of a complete anterior-superior radial tear of the labrum and bicep anchor instability has not been described in previous classifications of these injuries. The injury was traumatic in nature and was associated with a displaced fracture of the greater tuberosity. The labral pathology was treated by an anatomic repair technique as described. Rationale for the repair performed, as well as implications of the injury treated by debridement alone, are discussed. Clinicians should be aware of different patterns of superior labral-bicep complex injuries and the implications on function and stability of the glenohumeral joint.

Spinal cord injuries due to falls from hunting tree stands in Oklahoma, 1988-1999.

Serious injuries resulting in paralysis or death have been shown to occur to hunters who have sustained falls from tree stands. A total of sixteen spinal cord injuries or deaths among Oklahoma hunters falling from tree stands were reported between 1987 and 1999. The mean height of the falls was 16.4 feet. Three (18.8%) of the cases were related to substance use. None of the patients were using a safety restraint. Nearly 90% of the injuries resulted in paraplegia/paresis; two (12.5%) of the injuries resulted in death. Forty-four percent of the spinal injuries occurred at the thoraco-lumbor junction (T12 or L1). Burst fractures were the most common fracture pattern. Hospitalizations averaged 19.6 days (range 3 to 73 days) and eight (50%) were discharged to inpatient rehabilitation facilities. Falls from tree stands can result in serious injuries or death. Hunter education and the use of safety harnesses for prevention of injuries related to tree stands are paramount.

Bound magnetic polarons in the 3d-electron ferromagnetic spinel semiconductor CdCr2Se4.

Muon spin rotation/relaxation spectroscopy has been employed to study electron localization into a bound magnetic polaron around the positive muon in the 3d magnetic spinel semiconductor CdCr2Se4 at temperatures up to 300 K (far above the ferromagnetic transition at Tc = 130 K) in magnetic fields up to 7 T. Electron localization into a magnetic polaron occurs due to its strong exchange interaction with the magnetic 3d electrons of local Cr(3 +) ions, which confines its wavefunction to within R≈0.3 nm, allowing significant overlap with both the nearest and the next nearest shells of Cr ions. Formation of such magnetic polarons may explain peculiar electronic and magnetic properties of magnetic semiconductors.