Trap-Assisted Complexes in Cold Atom-Ion Collisions.

We theoretically investigate the trap-assisted formation of complexes in atom-ion collisions and their impact on the stability of the trapped ion. The time-dependent potential of the Paul trap facilitates the formation of temporary complexes by reducing the energy of the atom, which gets temporarily stuck in the atom-ion potential. As a result, those complexes significantly impact termolecular reactions leading to molecular ion formation via three-body recombination. We find that complex formation is more pronounced in systems with heavy atoms, but the mass has no influence on the lifetime of the transient state. Instead, the complex formation rate strongly depends on the amplitude of the ion's micromotion. We also show that complex formation persists even in the case of a time-independent harmonic trap. In this case, we find higher formation rates and longer lifetimes than in Paul traps, indicating that the atom-ion complex plays an essential role in atom-ion mixtures in optical traps.

Observation of Chemical Reactions between a Trapped Ion and Ultracold Feshbach Dimers.

We measure chemical reactions between a single trapped ^{174}Yb^{+} ion and ultracold Li_{2} dimers. This produces LiYb^{+} molecular ions that we detect via mass spectrometry. We explain the reaction rates by modeling the dimer density as a function of the magnetic field and obtain excellent agreement when we assume the reaction to follow the Langevin rate. Our results present a novel approach towards the creation of cold molecular ions and point to the exploration of ultracold chemistry in ion molecule collisions. What is more, with a detection sensitivity below molecule densities of 10^{14} m^{-3}, we provide a new method to detect low-density molecular gases.

Trapped Ion Quantum Computing Using Optical Tweezers and Electric Fields.

We propose a new scalable architecture for trapped ion quantum computing that combines optical tweezers delivering qubit state-dependent local potentials with oscillating electric fields. Since the electric field allows for long-range qubit-qubit interactions mediated by the center-of-mass motion of the ion crystal alone, it is inherently scalable to large ion crystals. Furthermore, our proposed scheme does not rely on either ground-state cooling or the Lamb-Dicke approximation. We study the effects of imperfect cooling of the ion crystal, as well as the role of unwanted qubit-motion entanglement, and discuss the prospects of implementing the state-dependent tweezers in the laboratory.

Verification of a Many-Ion Simulator of the Dicke Model Through Slow Quenches across a Phase Transition.

We use a self-assembled two-dimensional Coulomb crystal of ∼70 ions in the presence of an external transverse field to engineer a simulator of the Dicke Hamiltonian, an iconic model in quantum optics which features a quantum phase transition between a superradiant (ferromagnetic) and a normal (paramagnetic) phase. We experimentally implement slow quenches across the quantum critical point and benchmark the dynamics and the performance of the simulator through extensive theory-experiment comparisons which show excellent agreement. The implementation of the Dicke model in fully controllable trapped ion arrays can open a path for the generation of highly entangled states useful for enhanced metrology and the observation of scrambling and quantum chaos in a many-body system.

First-order phase transitions in optical lattices with tunable three-body onsite interaction.

We study the two-dimensional Bose-Hubbard model in the presence of a three-body interaction term, both at a mean-field level and via quantum Monte Carlo simulations. The three-body term is tuned by coupling the triply occupied states to a trapped universal trimer. We find that, for a sufficiently attractive three-body interaction, the n=2 Mott lobe disappears and the system displays first-order phase transitions separating the n=1 from the n=3 lobes and the n=1 and n=3 Mott insulator from the superfluid. We also analyze the effect of finite temperature and find that transitions are still of first order at temperatures T~J, where J is the hopping matrix element.

Author Correction: Unifying scrambling, thermalization and entanglement through measurement of fidelity out-of-time-order correlators in the Dicke model.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Unifying scrambling, thermalization and entanglement through measurement of fidelity out-of-time-order correlators in the Dicke model.

Scrambling is the process by which information stored in local degrees of freedom spreads over the many-body degrees of freedom of a quantum system, becoming inaccessible to local probes and apparently lost. Scrambling and entanglement can reconcile seemingly unrelated behaviors including thermalization of isolated quantum systems and information loss in black holes. Here, we demonstrate that fidelity out-of-time-order correlators (FOTOCs) can elucidate connections between scrambling, entanglement, ergodicity and quantum chaos (butterfly effect). We compute FOTOCs for the paradigmatic Dicke model, and show they can measure subsystem Rényi entropies and inform about quantum thermalization. Moreover, we illustrate why FOTOCs give access to a simple relation between quantum and classical Lyapunov exponents in a chaotic system without finite-size effects. Our results open a path to experimental use FOTOCs to explore scrambling, bounds on quantum information processing and investigation of black hole analogs in controllable quantum systems.

Human CoQ10 deficiencies.

Coenzyme Q10 (CoQ10 or ubiquinone) is a lipid-soluble component of virtually all cell membranes and has multiple metabolic functions. A major function of CoQ10 is to transport electrons from complexes I and II to complex III in the respiratory chain which resides in the mitochondrial inner membrane. Deficiencies of CoQ10 (MIM 607426) have been associated with four major clinical phenotypes: 1) encephalomyopathy characterized by a triad of recurrent myoglobinuria, brain involvement, and ragged-red fibers; 2) infantile multisystemic disease typically with prominent nephropathy and encephalopathy; 3) cerebellar ataxia with marked cerebellar atrophy; and 4) pure myopathy. Primary CoQ10 deficiencies due to mutations in ubiquinone biosynthetic genes (COQ2, PDSS1, PDSS2, and ADCK3 [CABC1]) have been identified in patients with the infantile multisystemic and cerebellar ataxic phenotypes. In contrast, secondary CoQ10 deficiencies, due to mutations in genes not directly related to ubiquinone biosynthesis (APTX, ETFDH, and BRAF), have been identified in patients with cerebellar ataxia, pure myopathy, and cardiofaciocutaneous syndrome. In many patients with CoQ10 deficiencies, the causative molecular genetic defects remain unknown; therefore, it is likely that mutations in additional genes will be identified as causes of CoQ10 deficiencies.

Double-blind parallel design pilot study of acetyl levocarnitine in patients with Alzheimer's disease.

Acetyl levocarnitine hydrochloride has been reported to retard dementia in patients with Alzheimer's disease. In a double-blind, parallel design, placebo-controlled pilot study of 30 mild to moderately demented patients with probable Alzheimer's disease, tests of memory, attention, language, visuospatial, and constructional abilities were administered, and the level of acetyl levocarnitine was measured in the cerebrospinal fluid. Patients were then randomly assigned to receive acetyl levocarnitine hydrochloride (2.5 g/d for 3 months followed by 3 g/d for 3 months) or placebo. After 6 months, the acetyl levocarnitine group demonstrated significantly less deterioration in timed cancellation tasks and Digit Span (forward) and a trend toward less deterioration in a timed verbal fluency task. No differences were found in any other neuropsychological test results. A subgroup with the lowest baseline scores, receiving acetyl levocarnitine, had significantly less deterioration on the verbal memory test and a significant increase in cerebrospinal fluid acetyl levocarnitine levels compared with those receiving placebo. These results suggest that acetyl levocarnitine may retard the deterioration in some cognitive areas in patients with Alzheimer's disease and stress the need for a larger study of this drug.

Stereotaxic implantation of autologous adrenal medulla into caudate nucleus in four patients with parkinsonism. One-year follow-up.

Four patients with levodopa-responsive parkinsonism (aged 26, 35, 45, and 49 years) received autologous adrenal medullary implants into or near the left caudate nucleus by stereotaxic implantation after flank adrenalectomy. All patients had an immediate response to implantation lasting several days, during which parkinsonian signs and symptoms decreased. This period was followed by a gradual reappearance of symptoms in all but one patient. This patient had had a dramatic increase in "on" time without dyskinesias and a decrease in the severity and duration of "off" time. He died of multifocal glioblastoma 1 year after transplantation. Autopsy revealed no surviving adrenal cells. In one case, the stereotaxic implantation missed the basal ganglia, resulting in the placement of the adrenal medullary tissue into the medial thalamus and near the third ventricle; the patient did not improve. In the other two cases, a modest but definite increase in "on" time without dyskinesia and a reduction in the severity and duration of "off" time has been observed. The role of autologous adrenal medullary transplantation in patients with parkinsonism remains to be determined. Patients with a family history of cerebral malignancy may be at increased risk for the development of transplant-induced malignancy.

CADASIL in a North American family: clinical, pathologic, and radiologic findings.

OBJECTIVE: To expand the reported phenotypic range of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). BACKGROUND: Despite numerous patient reports, our knowledge of the phenotypic range of CADASIL remains incomplete. METHOD: We performed clinical, pathologic, and radiologic examinations on members of a family with CADASIL. RESULTS: The proband is a 61-year-old man with a history of migraine and depression who has experienced multiple subcortical infarctions resulting in a stepwise decline. Neuropsychological testing documented a dementia syndrome with frontal lobe features and neurologic examination noted a left hemiparesis and a right-sided palmomental reflex. Brain biopsy with light microscopy revealed a nonatherosclerotic small-vessel angiopathy with periodic acid-Schiff positive granular changes in the media and white matter gliosis, with unremarkable cortex. Genetic testing confirmed a Notch3 mutation. The proband's first cousin has a history of depression, one seizure possibly resulting from an acute stroke, and a learning disorder. Neuropsychological testing demonstrated deficits in executive function and neurologic examination noted persistent extraneous adventitial movements, poor coordination, and primitive reflexes. Skin biopsy with electron microscopy demonstrated granular osmiophilic material within the basement membrane of vascular smooth muscle cells, which is considered to be pathognomonic of CADASIL. The proband's older son and younger son have histories of migraine and depression, respectively, and both also had learning disorders. MRI revealed diffuse white matter disease extending into the temporal lobes, and lacunar infarctions in these four nonhypertensive patients. Other family members have experienced migraine, recurrent stroke, dementia, and depression. CONCLUSIONS: CADASIL is a genetic basis for vascular dementia that may be manifest earlier in life than previously reported.

Striatal D2 receptors in symptomatic and asymptomatic carriers of dopa-responsive dystonia measured with [11C]-raclopride and positron-emission tomography.

We tested the hypothesis that asymptomatic carriers of dopa-responsive dystonia (DRD) have increased dopamine D2 receptors in the striatum that protect them from the clinical manifestations of dopaminergic deficiency. We examined striatal D2-receptor binding in (1) symptomatic subjects (treated and untreated) and (2) asymptomatic gene carriers. Using [11C]-raclopride PET, we found elevated striatal D2-receptor binding in both groups. In one of our drug-naive symptomatic subjects, 7 months of treatment with levodopa/carbidopa did not affect the receptor binding as measured on a second scan. We conclude that increased D2-receptor binding in DRD may be a homeostatic response to the dopaminergic deficit in subjects carrying the DRD gene, but is not the sole factor determining the clinical state of these individuals.

Familial cerebellar ataxia with muscle coenzyme Q10 deficiency.

OBJECTIVE: To describe a clinical syndrome of cerebellar ataxia associated with muscle coenzyme Q10 (CoQ10) deficiency. BACKGROUND: Muscle CoQ10 deficiency has been reported only in a few patients with a mitochondrial encephalomyopathy characterized by 1) recurrent myoglobinuria; 2) brain involvement (seizures, ataxia, mental retardation), and 3) ragged-red fibers and lipid storage in the muscle biopsy. METHODS: Having found decreased CoQ10 levels in muscle from a patient with unclassified familial cerebellar ataxia, the authors measured CoQ10 in muscle biopsies from other patients in whom cerebellar ataxia could not be attributed to known genetic causes. RESULTS: The authors found muscle CoQ10 deficiency (26 to 35% of normal) in six patients with cerebellar ataxia, pyramidal signs, and seizures. All six patients responded to CoQ10 supplementation; strength increased, ataxia improved, and seizures became less frequent. CONCLUSIONS: Primary CoQ10 deficiency is a potentially important cause of familial ataxia and should be considered in the differential diagnosis of this condition because CoQ10 administration seems to improve the clinical picture.

Mitochondrial DNA depletion: mutations in thymidine kinase gene with myopathy and SMA.

BACKGROUND: The mitochondrial DNA (mtDNA) depletion syndrome (MDS) is an autosomal recessive disorder of early childhood characterized by decreased mtDNA copy number in affected tissues. Recently, MDS has been linked to mutations in two genes involved in deoxyribonucleotide (dNTP) metabolism: thymidine kinase 2 (TK2) and deoxy-guanosine kinase (dGK). Mutations in TK2 have been associated with the myopathic form of MDS, and mutations in dGK with the hepatoencephalopathic form. OBJECTIVES: To further characterize the frequency and clinical spectrum of these mutations, the authors screened 20 patients with myopathic MDS. RESULTS: No patient had dGK gene mutations, but four patients from two families had TK2 mutations. Two siblings were compound heterozygous for a previously reported H90N mutation and a novel T77M mutation. The other siblings harbored a homozygous I22M mutation, and one of them had evidence of lower motor neuron disease. The pathogenicity of these mutations was confirmed by reduced TK2 activity in muscle (28% to 37% of controls). CONCLUSIONS: These results show that the clinical expression of TK2 mutations is not limited to myopathy and that the myopathic form of MDS is genetically heterogeneous.

Interaction of Ca2(+)-activated K+ channels with refolded charybdotoxins mutated at a central interaction residue.

Charybdotoxin is a small peptide blocker of K+ channels, rigidly held in active conformation by three disulfide bonds. The toxin blocks K+ channels by binding to a receptor site located at the external "vestibule", and thus physically occluding the outer opening of the K+ conduction pore. In the blocked complex, K27, a residue on the toxin's molecular surface, projects its epsilon-amino group into the K(+)-selective pore. The results here show that CTX, produced by heterologous expression in E. coli, may be manipulated to place unnatural positively charged residues at position 27. The toxin folds faithfully to its native conformation when the crucial lysine at position 27 is replaced by a cysteine residue, a maneuver that allows specific chemical modification of this side-chain. Replacements of K27 by side-chains slightly shorter or slightly longer than lysine yield active toxins. The toxin variant with ornithine at this position interacts much less strongly with K+ ions in the pore of slowpoke-type Ca2(+)-activated K+ channels than does wild-type toxin. This result argues that the epsilon-amino group of K27 in bound toxin lies only a few ångstroms away from a K+ ion occupying the blocked pore. The peptide folds with high efficiency to form the correct disulfides even in the presence of strong denaturants.

Augmented pharmacologic stimulation of striatal acetylcholine release following developmental hypoxic-ischemic injury.

We have previously shown that developmental hypoxic-ischemic injury in a unilateral rodent model leads to an increase in both morphologic and biochemical indices of striatal cholinergic neurons. To investigate the functional significance these changes, we have used the in vivo microdialysis technique to examine the regulation of striatal acetylcholine release in awake, adult rats following postnatal hypoxic-ischemic injury. We have found that injury does not alter basal release or acetylcholine, but it results in a marked augmentation in the increase of acetylcholine release normally observed after infusion of atropine or pirenzepine.

Identification of a novel mutation in Cu/Zn superoxide dismutase gene associated with familial amyotrophic lateral sclerosis.

We report a new missense mutation (Ala140Gly) in exon 5 of the Cu/Zn superoxide dismutase (SOD-1) gene in a 73-year-old man with familial amyotrophic lateral sclerosis (FALS). The enzymatic activity of mutated SOD-1 measured in erythrocyte lysate was 70% of control. This heterozygote mutation, which is associated with the late onset of the disease, is located in the active site of the enzyme.

Dopa-responsive dystonia simulating cerebral palsy.

Five patients presented in infancy or early childhood with various combinations of pyramidal and extrapyramidal signs with normal cognitive function. Their perinatal courses were unremarkable. In each patient, initial impressions listed by several examiners included spastic diplegia or cerebral palsy. Later in each course, either extrapyramidal features or progression suggested dopa-responsive dystonia. In 4 of the 5 children, cerebrospinal fluid was obtained and disclosed reduced levels of biopterin, neopterin, and homovanillic acid in all 4. Levodopa therapy resulted in prompt improvement with normal function returning within 6 months. The disappearance of the "spasticity," extensor plantar responses, and extrapyramidal signs, following levodopa therapy, confirmed the diagnosis of doparesponsive dystonia in these patients. Three had apparently sporadic disease; the other 2 were siblings with an affected paternal grandmother. Three had onset in infancy with delayed sitting and walking before the appearance of overt dystonia; infantile onset is infrequent in dopa-responsive dystonia. The other 2 had normal milestones, but developed gait disorders with prominent imbalance in early childhood. The diagnosis of dopa-responsive dystonia should be considered in children with unexplained or atypical "cerebral palsy."

Endotoxin levels in periodontally healthy and diseased sites: correlation with levels of gram-negative bacteria.

This study investigated the correlation between endotoxin levels and the percentage of Gram-negative bacteria in healthy sites and in periodontitis sites. Twelve healthy adults participated. Each subject provided 3 periodontitis sites with 5 to 8 mm probing depths that bled on gentle probing and 3 healthy sites with sulcus depths of 1 to 3 mm that did not bleed. Clinical examinations and sterile paper point sampling of all study sites were conducted on days 0, 7, and 14, and site-specific endotoxin levels and percentage of Gram-negative bacteria were determined. There were significant differences in both endotoxin levels and percentage Gram-negative bacteria between healthy and periodontitis sites across all 3 sampling periods, but no difference across sampling periods in the healthy sites and the periodontitis sites, respectively. Correlation coefficients revealed a high degree of correlation between site-specific endotoxin levels and percentage of Gram-negative organisms. Using a sample dilution of 1 x 10(4), endotoxin levels differentiated healthy from periodontitis sites with a specificity of approximately 91% and a sensitivity of approximately 90%.

Effect of protein malnutrition on the composition of submandibular glands of aged rats.

Fifty 22-month-old male Sprague-Dawley rats were fed for 8 weeks ad libitum with either a 20% protein diet (control) or a 5% protein diet (protein malnourished group). Submandibular glands were removed, weighed and homogenate prepared. After the low protein diet, there was a slight but significant decrease in body weight, glandular content of total protein (mg/g tissue), kallikrein activity/mg protein and glutamine-rich peptide. In contrast, the gland weight, DNA and mucin content were not changed by feeding a low protein diet. Thus in aged rats submandibular glands are only modestly affected by protein malnutrition and the effects on gland-specific proteins vary.