Coherent Control and Spectroscopy of a Semiconductor Quantum Dot Wigner Molecule.

Semiconductor quantum dots containing more than one electron have found wide application in qubits, where they enable readout and enhance polarizability. However, coherent control in such dots has typically been restricted to only the lowest two levels, and such control in the strongly interacting regime has not been realized. Here we report quantum control of eight different transitions in a silicon-based quantum dot. We use qubit readout to perform spectroscopy, revealing a dense set of energy levels with characteristic spacing far smaller than the single-particle energy. By comparing with full configuration interaction calculations, we argue that the dense set of levels arises from Wigner-molecule physics.

Communication: Nonadditive dielectric susceptibility spectra of associating liquids.

Highly unusual linear-response spectra involving contributions from hydrogen-bonded supramolecular processes and from structural relaxations are found in 4-methyl-3-heptanol mixed with 2-ethyl-1-hexylbromide. Although the mean time scales of the underlying relaxations are separated by more than 3 decades, the overall spectra cannot be decomposed into a sum of these processes. This finding challenges the ubiquitous practice of disentangling susceptibility spectra of Debye liquids by adding suitable subspectra. The spectral shape of the studied viscous mixtures is excellently described using the Williams ansatz, here a necessary approach and not as previously considered merely an alternative to additive analyses.

Characterization of a gate-defined double quantum dot in a Si/SiGe nanomembrane.

We report the fabrication and characterization of a gate-defined double quantum dot formed in a Si/SiGe nanomembrane. In the past, all gate-defined quantum dots in Si/SiGe heterostructures were formed on top of strain-graded virtual substrates. The strain grading process necessarily introduces misfit dislocations into a heterostructure, and these defects introduce lateral strain inhomogeneities, mosaic tilt, and threading dislocations. The use of a SiGe nanomembrane as the virtual substrate enables the strain relaxation to be entirely elastic, eliminating the need for misfit dislocations. However, in this approach the formation of the heterostructure is more complicated, involving two separate epitaxial growth procedures separated by a wet-transfer process that results in a buried non-epitaxial interface 625 nm from the quantum dot. We demonstrate that in spite of this buried interface in close proximity to the device, a double quantum dot can be formed that is controllable enough to enable tuning of the inter-dot tunnel coupling, the identification of spin states, and the measurement of a singlet-to-triplet transition as a function of an applied magnetic field.

A genetically encoded, fluorescent indicator for cyclic AMP in living cells.

Cyclic AMP controls several signalling cascades within cells, and changes in the amounts of this second messenger have an essential role in many cellular events. Here we describe a new methodology for monitoring the fluctuations of cAMP in living cells. By tagging the cAMP effector protein kinase A with two suitable green fluorescent protein mutants, we have generated a probe in which the fluorescence resonance energy transfer between the two fluorescent moieties is dependent on the levels of cAMP. This new methodology opens the way to the elucidation of the biochemistry of cAMP in vivo.

Quantitation of transcription and clonal selection of single living cells with beta-lactamase as reporter.

Gene expression was visualized in single living mammalian cells with beta-lactamase as a reporter that hydrolyzes a substrate loaded intracellularly as a membrane-permeant ester. Each enzyme molecule changed the fluorescence of many substrate molecules from green to blue by disrupting resonance energy transfer. This wavelength shift was detectable by eye or color film in individual cells containing less than 100 beta-lactamase molecules. The robust change in emission ratio reveals quantitative heterogeneity in real-time gene expression, enables clonal selection by flow cytometry, and forms a basis for high-throughput screening of pharmaceutical candidate drugs in living mammalian cells.

Progress in reducing the pale, soft and exudative (PSE) problem in pork and poultry meat.

Research in the area of the pale, soft and exudative (PSE) pork and poultry meat is reviewed in this article with an emphasis on genetic, biochemical and metabolic factors contributing to the problem. Over the past five decades, there has been much more work in the pork meat area where a few genetic markers have been identified, and are currently used to remove susceptible animals from the herd. Some of the markers are linked to aberrant calcium regulation in the early postmortem muscle. The poultry industry is still not at the point of using genetic marker(s); however, some recent work has revealed several potential markers. The review also discusses environmental factors such as antemortem stress and early postmortem processing practices (e.g. chilling rate) that can influence the development and severity of the PSE phenomenon. Some of these factors are known to cause protein denaturation at the early stage of postmortem and directly contribute to poor water-holding capacity and inferior texture in fresh meat and later in processed products. A newer hypothesis suggesting that variation in protein oxidation, in response to antemortem stress and early postmortem tissue environment, can contribute to development of PSE pork is also discussed. Finally, a few recommendations for future work are proposed.

A genome-wide functional assay of signal transduction in living mammalian cells.

We describe a genome-wide functional assay for rapid isolation of cell clones and genetic elements responsive to specific stimuli. A promoterless beta-lactamase reporter gene was transfected into a human T-cell line to generate a living library of reporter-tagged clones. When loaded with a cell-permeable fluorogenic substrate, the cell library simultaneously reports the expression of a large number of endogenous genes. Flow cytometry was used to recover individual clones whose reporter-tagged genes were either induced or repressed following T-cell activation. Responsive clones were expanded and analyzed pharmacologically to identify patterns of regulation associated with specific genes. Although demonstrated using T cells, the genomic assay could be applied to map downstream transcriptional consequences for any propagating cell line in response to any stimulus of interest.

Collagen-induced secretion-dependent phase of platelet aggregation is inhibited by the snake venom metalloproteinase jararhagin.

Jararhagin, a 52 kDa metalloproteinase from Bothrops jararaca snake venom, belongs to the family of enzymes with an N-terminal Zn2+-containing enzymatic domain, a disintegrin-like domain and a cysteine-rich C-terminal domain. Both jararhagin and jararhagin C, a 28 kDa-protein from the same venom identical to the disintegrin-like domain of jararhagin, inhibit collagen-induced platelet aggregation. In this study, jararhagin and synthetic linear peptides based on the disintegrin-like domain of jararhagin overlapping with the RGD sequence of venom disintegrins, were shown for the first time to inhibit the release of 5-hydroxytryptamine (5-HT) from platelets preloaded with [14C]5-HT and stimulated with collagen. The normal phosphorylation of the 21-kDa myosin light chain (p21) in response to the stimulation indicated that jararhagin and the peptides did not interfere with platelet shape change. The selective inhibition of the secretion-dependent phase of the platelet response to collagen by the enzyme and its peptides was confirmed by the defective phosphorylation of pleckstrin, a 47-kDa platelet protein (p47) involved in dense granule secretion.

Cloning of a polymorphic DNA fragment from the genome of Leishmania donovani.

Recombinant DNA clones, containing highly repetitive DNA sequences, have been isolated from a Leishmania donovani genomic DNA library prepared in the replacement vector lambda gt.WES.lambda B. Two clones, probably telomeric in location, have been characterised and show a restriction fragment size polymorphism. Evidence is presented which suggests that L. donovani is diploid for this cloned genomic locus.

Comparison of intravenous and oral antibiotic therapy in the treatment of fractures caused by low-velocity gunshots. A prospective, randomized study of infection rates.

One hundred and ninety consecutive patients (222 fractures) who had an extra-articular fracture of a long bone as a result of a low-velocity gunshot were randomized into two groups on the basis of the method of administration of antibiotics. Group 1 consisted of 101 patients (120 fractures) who were managed with intravenous administration of cephapirin sodium and gentamicin for three days. Group 2 comprised eighty-nine patients (102 fractures) who were managed with oral administration of ciprofloxacin for three days. The two groups were comparable in terms of the age of the patient, the locations of the fractures, and the time from the injury to the commencement of antibiotic therapy. Injuries that needed operative débridement or fixation were excluded. All patients were followed until the fracture had healed. Two infections developed in two of the ninety-nine patients (118 fractures) who completed the study in Group 1, and two infections developed in two of the eighty-seven patients (100 fractures) who completed the study in Group 2. With the numbers available, there was no significant difference in the rates of infection (2 per cent for both) between the two groups. All four fractures that were complicated by infection were located in the distal half of the tibia. We concluded that oral and intravenous administration of antibiotics were equally effective for prophylaxis against infection after an extra-articular fracture from a low-velocity gunshot.

Treating migraine by training in temporal artery vasoconstriction and/or cognitive behavioral coping: a one-year follow-up.

A one-year follow-up on 16 chronic migraine patients treated with vasoconstriction biofeedback of the temporal arteries (VT) or cognitive behavioral stress coping training (CT), or one of two serial variations of them, is reported: there were four experimental groups EG-1a: VT, 10 sessions; EG-1b: Vt, 5 sessions and CT, 5 sessions; EG-11a: CT, 10 sessions; EG-11b: CT, 5 sessions and VT, 5 sessions. Another group of 4 migraine patients was assigned to a waiting control. All treatment groups decreased the frequency, duration and intensity of headaches, as well as amount of medication from baseline to the one-year follow-up. However, there were no differences between the groups (the controls were not followed-up). During treatment, but not at follow-up 1 (two months after therapy), voluntary vasoconstriction was higher in EG-1a than in EG-11a, although all EGs vasoconstricted. Voluntary vasoconstriction was not tested at one-year follow-up. The cognitive training groups improved more in self-ratings of irritability, depression and positive self-evaluation than the biofeedback or control groups on follow-up 1, but this difference was not maintained at one year. All treatment groups showed deterioration in measure of excitement and depression, returning to pre-treatment levels. Improvements in irritability and positive-self-evaluation were however sustained at one year follow-up.

Emergence of resistance to clarithromycin during treatment of disseminated cutaneous Mycobacterium chelonae infection: case report and literature review.

Results of in vitro susceptibility studies and one clinical trial have led to recommendations of clarithromycin monotherapy for the treatment of disseminated cutaneous Mycobacterium chelonae infections. We describe the case of a 65-year-old woman, immunocompromised by the use of chronic steroid therapy, who developed disseminated cutaneous infection with M. chelonae and failed clarithromycin monotherapy due to the development of drug resistance. In the relapse isolate we document the presence of a single point mutation at position 2058 in the gene coding for 23S rRNA peptidyltransferase regions, a mutation previously implicated in the development of resistance to clarithromycin. Two susceptible control isolates lacked the mutation. Three additional reports in the literature of patients developing recurrent skin lesions with clarithromycin-resistant M. chelonae following initial response to monotherapy are summarized. We demonstrate that clarithromycin monotherapy in patients with disseminated cutaneous infections can lead to clarithromycin resistance and therapeutic failure associated with a single point mutation at position 2058 of 23S rRNA.

A controlled trial of imipramine for the treatment of methamphetamine dependence.

At the Drug Detoxification Program of the Haight Ashbury Free Clinics, we conducted a randomized clinical trial of imipramine in the treatment of methamphetamine dependence. The purposes of the trial were to test the efficacy of imipramine as a treatment for methamphetamine dependence and to establish the feasibility of conducting a controlled clinical trial at the Clinic. Thirty-two subjects were randomly assigned to receive either 10 or 150 mg/day of imiprine for 180 days. Imipramine 10 mg/day was the control. Subjects received intensive counseling. Retention in treatment was significantly longer for subjects who were treated with 150 mg of imipramine compared to control (median days: 33.0 vs. 10.5). There were no consistent differences in percent of urine samples positive for methamphetamine, Beck Depression Inventory scores, or craving. Determination of the full extent of imipramine's utility in the treatment of methamphetamine dependence awaits a larger trial.

The augmentation of soft tissue with injectable collagen.

Clinical experience has demonstrated the value of injectable collagen in treating small soft-tissue defects. Among the lesions that respond best to injectable collagen therapy are nasolabial and glabellar lines as well as areas of atrophy and soft scars. This material is a useful adjunct to surgical procedures and can correct contour irregularities that may follow rhinoplasty or rhytidectomy. The safety of injectable collagen has also been well demonstrated. The nature and incidence of treatment reactions (less than 3 per cent) remains unchanged since the close of clinical trials. Reactions have been localized, and although some have been cosmetically undesirable, none has been health-threatening. All ultimately resolve without therapeutic intervention. Immunologic studies have confirmed the benign nature and specificity of reactions to injectable collagen. The importance of proper injection technique cannot be overstated. Immediately upon injection, tissue blanching followed by whealing and overcorrection should be evident. These indicate the desired superficial placement of the material. The overcorrection helps to compensate for the loss of carrier saline, and it quickly dissipates. When properly injected, injectable collagen can be used safely and effectively to correct an array of soft-tissue contour irregularities.

Injectable collagen for soft tissue augmentation.

Collagen from allogenic and xenogeneic sources has been made soluble by controlled proteolytic digestion. The monomeric, telopeptide-poor collagen so prepared forms a cohesive mass when warmed to body temperature (upon injection), creating a structural basis for new soft connective tissue. We have treated 28 patients with human and/or bovine collagen injections for the correction of soft tissue contour defects, and we have followed them for 3 to 18 months. In most instances, there has been lasting and substantial correction of the defects treated. The complications have been few and transient.

Imipramine for the treatment of cocaine and methamphetamine dependence.

At the Drug Detoxification, Rehabilitation, and Aftercare Program of the Haight-Ashbury Free Clinics, we conducted a double-blind, controlled, randomized clinical trial of imipramine in the treatment of cocaine and methamphetamine abusers. The purpose of the trial was to test the efficacy of imipramine as a treatment for stimulant dependence and to establish the feasibility of conducting a controlled clinical trial at the clinic under conditions that approximated usual clinical practice. Subjects were randomly assigned to receive either 10 or 150 mg/day of imipramine. Imipramine 10 mg/day was the control condition. Subjects could receive study medication for up to 180 days. One-hundred eighty-three subjects participated in the study: 151 were cocaine dependent and 32 were methamphetamine dependent. In addition to receiving study medication, all subjects were assigned to intensive drug abuse counseling, which included an HIV education component. Using an intention-to-treat analysis, we found that retention in treatment was significantly longer for subjects who were treated with 150 mg of imipramine compared to control. However, we found no consistent differences between the two groups of subjects in Beck Depression Inventory scores, stimulant craving, self-report of time since last use of stimulants, or percent of urinalyses positive for stimulants. The feasibility of conducting a controlled, randomized clinical trial of medication for treatment of drug abuse was established for this community clinic setting.

Teaching an autistic child pedestrian skills.

An autistic child was taught pedestrian skills in a classroom by use of a model of the streets and the intersection she most often frequented. She manipulated a doll and verbalized what the doll was doing to get to the designated location. After mastering the pedestrian skills on the model, video recordings familiarized her with traffic at local intersections. She successfully generalized the pedestrian skills to the natural environment.

Is arm span an accurate measure of height in young and middle-age adults?

Height is used to determine many important clinical measurements, but height may be difficult or impossible to measure accurately in some patients. The purpose of this study is to determine the accuracy of arm span as a measure of height in young and middle-age adults. A sample of 83 people between the ages of 20 and 61 years participated in this anthropometric study. Height and arm span were measured with a metal rule. A prediction equation was derived from regression analysis. Arm span is a valid measure of height in young and middle-age adults, and the accuracy is improved when using the prediction equation.

Stress fractures: general concepts.

This article is an overview of the general concepts about stress fractures, including history, epidemiology, and cause. The proper diagnosis, confirmation studies, and treatment regimens are presented. Finally, the timing of the athlete's return to sports, with stress fracture prevention measures are reviewed.

Symptom use and self-regulation in type II diabetes.

A model of self-regulation that explains the health behavior of type II diabetic patients was tested by examining the use of symptoms as indicators of perceived blood glucose levels in 38 outpatients. Results of the study supported the self-regulation model by demonstrating that patients use symptoms to monitor blood glucose levels and to guide diabetes-related actions. Implications of the model for planning interventions with type II diabetes are discussed.