Active laser frequency stabilization using neutral praseodymium (Pr)

We present a new possibility for the active frequency stabilization of a laser using transitions in neutral praseodymium. Because of its five outer electrons, this element shows a high density of energy levels leading to an extremely line-rich excitation spectrum with more than 25000 known spectral lines ranging from the UV to the infrared. We demonstrate the active frequency stabilization of a diode laser on several praseodymium lines between 1105 and 1123 nm. The excitation signals were recorded in a hollow cathode lamp and observed via laser-induced fluorescence. These signals are strong enough to lock the diode laser onto most of the lines by using standard laser locking techniques. In this way, the frequency drifts of the unlocked laser of more than 30 MHz/h were eliminated and the laser frequency stabilized to within 1.4(1) MHz for averaging times >0.2 s. Frequency quadrupling the stabilized diode laser can produce frequency-stable UV-light in the range from 276 to 281 nm. In particular, using a strong hyperfine component of the praseodymium excitation line E = 16 502.616_7/2 cm^-1 -> E' = 25 442.742_9/2 cm^-1 at lambda = 1118.5397(4) nm makes it possible - after frequency quadruplication - to produce laser radiation at lambda/4 = 279.6349(1) nm, which can be used to excite the D2 line in Mg^+.Comment: 10 pages, 14 figure

Identification and characterization of mechanistically distinct inducers of gamma-globin transcription

Inhibition of HbS polymerization is a major target for therapeutic approaches in sickle cell anemia. Toward this goal, initial efforts at pharmacological elevation of fetal hemoglobin (HbF) has shown therapeutic efficacy. In order to identify well-tolerated, novel agents that induce HbF in patients, we developed a high-throughput screening approach based on induction of gamma-globin gene expression in erythroid cells. We measured gamma-globin transcription in K562 cells transfected with either gamma promoter elements fused with the locus control region hypersensitivity site 2 and luciferase reporter gene (HS2 gamma) or a beta-yeast artificial chromosome in which the luciferase reporter gene was recombined into the gamma-globin coding sequences (gamma YAC). Corresponding pharmacological increases in HbF protein were confirmed in both K562 cells and in human primary erythroid progenitor cells. Approximately 186,000 defined chemicals and fungal extracts were evaluated for their ability to increase gamma gene transcription in either HS2 gamma or gamma YAC models. Eleven distinct classes of compounds were identified, the majority of which were active within 24-48 hr. The short chain hydroxamate-containing class generally exhibited delayed maximal activity, which continued to increase transcription up to 120 hr. The cyclic tetrapeptide OSI-2040 and the hydroxamates were shown to have histone deacetylase inhibitory activity. In primary hematopoietic progenitor cell cultures, OSI-2040 increased HbF by 4.5-fold at a concentration of only 40 nM, comparable to the effects of hydroxyurea at 100 microM. This screening methodology successfully identifies active compounds for further mec

Linear Paul trap design for an optical clock with Coulomb crystals

We report on the design of a segmented linear Paul trap for optical clock applications using trapped ion Coulomb crystals. For an optical clock with an improved short-term stability and a fractional frequency uncertainty of 10^-18, we propose 115In+ ions sympathetically cooled by 172Yb+. We discuss the systematic frequency shifts of such a frequency standard. In particular, we elaborate on high precision calculations of the electric radiofrequency field of the ion trap using the finite element method. These calculations are used to find a scalable design with minimized excess micromotion of the ions at a level at which the corresponding second- order Doppler shift contributes less than 10^-18 to the relative uncertainty of the frequency standard

Comparison of cohesive powder flowability measured by Schulze Shear Cell, Raining Bed Method, Sevilla Powder Tester and new Ball Indentation Method

Poor powder flow leads to many problems during manufacturing and can lead to inaccurate dosing and off-specification products. Powder flowability is commonly assessed under relatively high applied loads using shear cells by characterising the unconfined yield strength at a range of applied loads. For applied stresses below 1 kPa, it becomes increasingly difficult to obtain reliable values of the unconfined yield strength. The bulk cohesion and tensile strength of the powder are then obtained by extrapolating the yield locus to zero and negative loads, respectively. However, the reliability of this approximation for a given material is not known. To overcome this limitation, techniques such as the Raining Bed Method, Sevilla Powder Tester and the newly-developed Ball Indentation Method may be used. In this paper, we report our measurement results of the tensile strength of glass beads, α-lactose monohydrate and various sizes of fluid catalytic cracking powders determined by the Sevilla Powder Tester and Raining Bed Method and compare them with those inferred from the Schulze Shear Cell. The results of the latter are also compared with those of the Ball Indentation Method. The outcome suggests that in the case of shear cell tests, the extrapolation of the yield locus to lower or negative loads is unsafe. The ball indentation method enables the characterisation of highly cohesive powders at very low compressive loads; however extrapolation to negative loads is still not reliable. In contrast, the Sevilla Powder Tester and Raining Bed Methods are able to characterise the tensile strength directly, but high bulk cohesion poses difficulties as the internal bed failure needs to be analysed in order to reliably estimate the tensile strength. These methods provide a better understanding of powder flow behaviour at low stresses, thus enabling a greater control of manufacturing processes

What are the basic self-monitoring components for cardiovascular risk management?

<p>Abstract</p> <p>Background</p> <p>Self-monitoring is increasingly recommended as a method of managing cardiovascular disease. However, the design, implementation and reproducibility of the self-monitoring interventions appear to vary considerably. We examined the interventions included in systematic reviews of self-monitoring for four clinical problems that increase cardiovascular disease risk.</p> <p>Methods</p> <p>We searched Medline and Cochrane databases for systematic reviews of self-monitoring for: heart failure, oral anticoagulation therapy, hypertension and type 2 diabetes. We extracted data using a pre-specified template for the identifiable components of the interventions for each disease. Data was also extracted on the theoretical basis of the education provided, the rationale given for the self-monitoring regime adopted and the compliance with the self-monitoring regime by the patients.</p> <p>Results</p> <p>From 52 randomized controlled trials (10,388 patients) we identified four main components in self-monitoring interventions: education, self-measurement, adjustment/adherence and contact with health professionals. Considerable variation in these components occurred across trials and conditions, and often components were poorly described. Few trials gave evidence-based rationales for the components included and self-measurement regimes adopted.</p> <p>Conclusions</p> <p>The components of self-monitoring interventions are not well defined despite current guidelines for self-monitoring in cardiovascular disease management. Few trials gave evidence-based rationales for the components included and self-measurement regimes adopted. We propose a checklist of factors to be considered in the design of self-monitoring interventions which may aid in the provision of an evidence-based rationale for each component as well as increase the reproducibility of effective interventions for clinicians and researchers.</p

Effects of self-monitoring of glucose in non-insulin treated patients with type 2 diabetes: design of the IN CONTROL-trial

<p>Abstract</p> <p>Background</p> <p>Diabetes specific emotional problems interfere with the demanding daily management of living with type 2 diabetes mellitus (T2DM). Possibly, offering direct feedback on diabetes management may diminish the presence of diabetes specific emotional problems and might enhance the patients' belief they are able to manage their illness. It is hypothesized that self-monitoring of glucose in combination with an algorithm how and when to act will motivate T2DM patients to become more active participants in their own care leading to a decrease in diabetes related distress and an increased self-efficacy.</p> <p>Methods and design</p> <p>Six hundred patients with T2DM (45 ≤ 75 years) who receive care in a structured diabetes care system, HbA1c ≥ 7.0%, and not using insulin will be recruited and randomized into 3 groups; Self-monitoring of Blood Glucose (SMBG), Self-monitoring of Urine Glucose (SMUG) and usual care (n = 200 per group). Participants are eligible if they have a known disease duration of over 1 year and have used SMBG or SMUG less than 3 times in the previous year. All 3 groups will receive standardized diabetes care. The intervention groups will receive additional instructions on how to perform self-monitoring of glucose and how to interpret the results. Main outcome measures are changes in diabetes specific emotional distress and self-efficacy. Secondary outcome measures include difference in HbA1c, patient satisfaction, occurrence of hypoglycaemia, physical activity, costs of direct and indirect healthcare and changes in illness beliefs.</p> <p>Discussion</p> <p>The IN CONTROL-trial is designed to explore whether feedback from self-monitoring of glucose in T2DM patients who do not require insulin can affect diabetes specific emotional distress and increase self-efficacy. Based on the self-regulation model it is hypothesized that glucose self-monitoring feedback changes illness perceptions, guiding the patient to reduce emotional responses to experienced threats, and influences the patients ability to perform and maintain self-management skills.</p> <p>Trial registration</p> <p>Current Controlled Trials ISRCTN84568563</p

Accessory gland as a site for prothoracicotropic hormone controlled ecdysone synthesis in adult male insects

Insect steroid hormones (ecdysteroids) are important for female reproduction in many insect species and are required for the initiation and coordination of vital developmental processes. Ecdysteroids are also important for adult male physiology and behavior, but their exact function and site of synthesis remains unclear, although previous studies suggest that the reproductive system may be their source. We have examined expression profiles of the ecdysteroidogenic Halloween genes, during development and in adults of the flour beetle Tribolium castaneum. Genes required for the biosynthesis of ecdysone (E), the precursor of the molting hormone 20-hydroxyecdysone (20E), are expressed in the tubular accessory glands (TAGs) of adult males. In contrast, expression of the gene encoding the enzyme mediating 20E synthesis was detected in the ovaries of females. Further, Spookiest (Spot), an enzyme presumably required for endowing tissues with competence to produce ecdysteroids, is male specific and predominantly expressed in the TAGs. We also show that prothoracicotropic hormone (PTTH), a regulator of E synthesis during larval development, regulates ecdysteroid levels in the adult stage in Drosophila melanogaster and the gene for its receptor Torso seems to be expressed specifically in the accessory glands of males. The composite results suggest strongly that the accessory glands of adult male insects are the main source of E, but not 20E. The finding of a possible male-specific source of E raises the possibility that E and 20E have sex-specific roles analogous to the vertebrate sex steroids, where males produce primarily testosterone, the precursor of estradiol. Furthermore this study provides the first evidence that PTTH regulates ecdysteroid synthesis in the adult stage and could explain the original finding that some adult insects are a rich source of PTTH