Caged ATP-fuel for bionanodevices

Micro- and nanodevices require the controlled delivery of energy to power a variety of processes. The current paradigm of connecting a miniaturized device to a set of macroscopic auxiliary devices, such as power supplies or pumps, for the delivery of electrical and mechanical energy needs to be replaced to enable the design of stand-alone integrated bionanodevices with applications in remote biosensing or nanomedicine. Biological nanomachines, such as the motor protein kinesin, can efficiently convert energy stored in chemical compounds, in particular adenosine 5'-triphosphate (ATP), into mechanical work. This ability is an attractive feature of hybrid devices powered by biomolecular motors, since it removes the need for the storage and conversion of electrical energy. The consequences are a simplified fabrication process and packaging, leading to higher yields and lower costs, and the broadening of the applications, which can now include field-deployable nanodevices. Here, the potential of caged ATP as fuel for such engineering applications is discussed. Caged ATP can be stored in the buffer solution of a bionanodevice, "uncaged" by UV light, and utilized as fuel by many enzymes to catalyze chemical changes or power active transport. We demonstrate that DMNPE-caged ATP can be stored in sufficient amounts in a typical device and that the activation can be triggered with a UV lamp or even sunlight.     

Stability and spectral behavior of grating-controlled activelymode-locked lasers

Amplitude, timing, and wavelength instabilities in a semiconductor mode-locked laser are studied experimentally and by using an accurate numerical model. It is shown that these instabilities can occur when the RF drive frequency is tuned to give a minimum average pulsewidth. It is shown that experimental measurement techniques, such as sampling and averaging, can mask these instabilities. Using this numerical model, it is shown that the wavelength instability is associated with the amplitude and timing instabilities and that the large broadening of the optical spectrum observed experimentally is caused by a cyclic wavelength instability     

Influence of dietary sodium bicarbonate on the potassium metabolism of growing dairy calves.

We evaluated the influence of supplemental dietary NaHCO3 on K metabolism of young dairy calves. Thirty-two Holstein and Jersey male and female calves were blocked at 56 to 70 d after birth according to breed, sex, and age and assigned randomly to a 2 x 2 factorial arrangement of dietary treatments for 8 wk: .4% K with 0% NaHCO3, .4% K with 2% NaHCO3, .6% K with 0% NaHCO3, and .6% K with 2% NaHCO3. Feed intake was not affected by dietary KCl or NaHCO3 supplementation, but average daily gain increased with increased K and tended to be reduced by dietary NaHCO3. Plasma K was elevated by increased dietary K but generally was unaffected by NaHCO3. Urinary Ca excretion appeared to be reduced by NaHCO3; urine pH increased with supplemental NaHCO3. Results indicate 1) the K requirement of the growing calf is between .40 and .55% of diet DM, 2) because urinary K excretion was elevated by dietary NaHCO3, the K requirement may be increased when the diet is supplemented with NaHCO3, and 3) average daily gain and plasma K are sensitive indicators of dietary K in the growing calf.     

Responsiveness of self-reported and objective measures of disease severity in carpal tunnel syndrome

Responsiveness, the ability to detect meaningful clinical change, is a critical attribute of instruments used to evaluate outcomes of treatments. The authors hypothesized that self-administered symptom severity and functional status questionnaires are more responsive to clinical improvement after carpal tunnel release than traditional physical examination measures of strength and sensibility. Data were obtained from a randomized clinical trial of endoscopic versus open carpal tunnel release conducted in four university medical centers. Patients were evaluated before surgery and 3 months after surgery. Seventy-four patients indicating that they were more than 80% satisfied with the results of surgery were assumed to have clinically meaningful improvement and were the focus of the analysis. Evaluations included questionnaires assessing symptom severity, functional status, and activities of daily living as well as measurement of grip, pinch, and abductor pollicus brevis strength, and 2-point discrimination and Semmes-Weinstein pressure sensibility. Responsiveness was calculated with the standardized response mean (mean change/standard deviation of change) as well as the effect size (mean change/standard deviation of baseline values). The symptom severity scale was four times as responsive, and the functional status and activities of daily living scales were twice as responsive, as the measures of strength and sensibility. Self-administered symptom severity and functional status scales are much more responsive to clinical improvement than measures of neuromuscular impairment and should severe as primary outcomes in clinical studies of therapy for carpal tunnel syndrome.     

Evaluation of the aortic root by MRI: insights from patients with homozygous familial hypercholesterolemia

Hepatitis C chronically infects approximately 1.5% of Americans and is the most common clinical problem facing hepatologists. Since the virus was initially described in 1989, development of an effective therapy has been challenging. Although several different therapeutic agents have been used, no therapy has been shown to reliably eradicate the virus. Interferon-alpha, a cytokine with immunostimulatory and anti-viral properties, has become the therapy of choice for patients with chronic hepatitis C infection. Trials assessing the efficacy of interferon-alpha have characterized host and viral factors predictive of responses to treatment. A thorough understanding of these predictive factors is requisite to providing cost-effective therapeutic decisions for the patient with chronic hepatitis C infection.     

Cdc34 and the F-box protein Met30 are required for degradation of the Cdk-inhibitory kinase Swe1

Ubiquitin-mediated proteolysis controls the abundance of many cell cycle regulatory proteins. Recent work in Saccharomyces cerevisiae suggests that a complex consisting of Cdc53, Skp1, and a third component known as an F-box protein (termed SCF) in combination with Cdc34 specifically targets regulatory proteins for degradation, and that substrate specificity is likely to be mediated by the F-box subunit. A screen for genetic interactions with a cdc34 mutation yielded MET30, which encodes an F-box protein. MET30 is an essential gene required for cell cycle progression and met30 mutations interact genetically with mutations in SCF components. Furthermore, physical interactions between Met30, Cdc53, Cdc34, and Skp1 in vivo provide evidence for an SCFMet30 complex. We demonstrate the involvement of Met30 in the degradation of the Cdk-inhibitory kinase Swe1. Swe1 is stabilized in met30 mutants and GST-Met30 pull-down experiments reveal that Met30 specifically binds Swe1 in vivo. Furthermore, extracts prepared from cdc34 or met30 mutants are defective in polyubiquitination of Swe1. Taken together, these data suggest that SCF-mediated proteolysis may contribute to the regulation of entry into mitosis. Our data, in combination with previously published results, also provide evidence for distinct SCF complexes in vivo and support the idea that their F-box subunits mediate SCF substrate specificity.