Monitoring serum insulin-like growth factor-I (IGF-I), IGF binding protein-3 (IGFBP-3), IGF-I/IGFBP-3 molar ratio and leptin during growth hormone treatment for disordered growth

OBJECTIVE: Serum IGF-I levels are monitored during GH replacement treatment in adults with GH defi- ciency (GHD) to guide GH dose adjustment and to minimize occurrence of GH-related side-effects. This is not routine practice in children treated with GH. The aim of this study was to evaluate changes in (1) serum IGF-I, IGFBP-3 and IGF-I/IGFBP-3 molar ratio, and (2) serum leptin, an indirect marker of GH response, during the first year of GH treatment in children with disordered growth. DESIGN: An observational prospective longitudinal study with serial measurements at five time points during the first year of GH treatment was carried out. Each patient served as his/her own control. PATIENTS The study included 31 patients, grouped as (1) GHD (n=20) and (2) non-GHD (Turner syndrome n=7; Noonan syndrome n=4), who had not previously received GH treatment. MEASUREMENTS: Serum IGF-I, IGFBP-3 and leptin levels were measured before treatment and after 6 weeks, 3 months, 6 months and 12 months of GH treatment, with a mean dose of 0.5 IU/kg/wk in GHD and 0.7 IU/kg/wk in non-GHD groups. IGF-I, IGFBP-3 and the calculated IGF-I/IGFBP-3 molar ratio were expressed as SD scores using reference values from the local population. RESULTS: In the GHD group, IGF-I SDS before treatment was lower compared with the non-GHD (-5.4 ± 2.5 vs. -1.8 ± 1.0; P < 0.001). IGF-I (-1.8 SDS ± 2.2) and IGFBP-3 (-1.1 SDS ± 0.6) levels and their molar ratios were highest at 6 weeks and remained relatively constant thereafter. In the non-GHD group, IGF-I levels increased throughout the year and were maximum at 12 months (0.3 SDS ± 1.4) while IGFBP-3 (1.1 SDS ± 0.9) and IGF-I/IGFBP-3 molar ratio peaked at 6 months. In both groups, IGF-I SDS and IGF-I/IGFBP-3 during treatment correlated with the dose of GH expressed as IU/m2/week (r-values 0.77 to 0.89; P = 0.005) but not as IU/kg/week. Serum leptin levels decreased significantly during GH treatment in the GHD (median before treatment 4.0 g/l; median after 12 months treatment 2.4 g/l; P = 0.02) but not the non-GHD (median before treatment 3.0 g/l; median after 12 months treatment 2.6 g/l). In the GHD group, serum leptin before treatment correlated with 12 month change in height SDS (r = 0.70, P = 0.02). CONCLUSIONS: The pattern of IGF-I, IGFBP-3 and their molar ratio during the first year of GH treatment differed between the GHD and non-GHD groups. Calculation of GH dose by surface area may be preferable to calculating by body weight. As a GH dose-dependent increase in serum IGF-I and IGF-I/IGFBP-3 may be associated with adverse effects, serum IGF-I and IGFBP-3 should be monitored routinely during longterm GH treatment. Serum leptin was the only variable that correlated with first year growth response in GHD

A low cost, rapid impedance measurement technique suitable for Li-ion health diagnosis in battery energy storage systems

Battery energy storage is becoming a vital part of green energy systems. Prediction of the state of health of energy storage systems is difficult as it relies on a number of parameters. Pseudo Random Binary Sequence (PRBS) excitation of energy storage batteries has been shown to be a valid method of battery parameter identification for lead acid batteries [1]. The purpose of this work is to validate PRBS test data from a 3Ah LiFePO4 cell forming part of an EV battery-pack cell against Electrochemical Impedance Spectroscopy (EIS) data obtained from an industry-standard potentiostat (Solartron 1480). PRBS results are obtained in under 200 seconds on easily reproducible equipment which can be built into a green energy battery management system, while the EIS process takes over two hours on prohibitively expensive laboratory equipment. This work validates PRBS as a fast and portable method of obtaining the impedance spectrum of Lithium Ion cells, which can then be used to obtain information about SoH of the BESS

Design and Testing of High Current, High Voltage, Hexapolar Flexible Cables for Pulsed Power Applications

Under Defense Advanced Research Projects Agency (DARPA) and U. S. Army sponsorship, the Center for Electromechanics has designed and is constructing highly flexible, high current and voltage, magnetically compensated (hexapolar) cables and cable terminations as component interconnect buswork for a stand-alone, Compulsator-driven electromagnetic (EM) gun system. Flexible cables under development are rated at 300 kA peak current and peak voltage of 15 kV. Cable construction in this configuration provides several advantages; high flexibility, outstanding insulation integrity, ease in termination, and large conductor net cross sectional area (fig. 1). Standardized modular cable terminations are also being developed featuring compact construction, small footprint, a unique single-bolt (per polarity) high contact area/pressure electrical terminal, and electromagnetically self supporting high voltage insulated casing. The cable termination mates to a simply machined receptacle. Presented are cable and termination design criteria, cable parallel operation simulations and preliminary performance test data collected. A list of vendors capable of manufacturing the cables and terminations is also included.Center for Electromechanic

Genetic determinants of cellular addiction to DNA polymerase theta

Polymerase theta (Pol θ, gene name Polq) is a widely conserved DNA polymerase that mediates a microhomology-mediated, error-prone, double strand break (DSB) repair pathway, referred to as Theta Mediated End Joining (TMEJ). Cells with homologous recombination deficiency are reliant on TMEJ for DSB repair. It is unknown whether deficiencies in other components of the DNA damage response (DDR) also result in Pol θ addiction. Here we use a CRISPR genetic screen to uncover 140 Polq synthetic lethal (PolqSL) genes, the majority of which were previously unknown. Functional analyses indicate that Pol θ/TMEJ addiction is associated with increased levels of replication-associated DSBs, regardless of the initial source of damage. We further demonstrate that approximately 30% of TCGA breast cancers have genetic alterations in PolqSL genes and exhibit genomic scars of Pol θ/TMEJ hyperactivity, thereby substantially expanding the subset of human cancers for which Pol θ inhibition represents a promising therapeutic strategy

The Impact of an Adapted Climbing Program on Children with Attention-Deficit/Hyperactivity Disorder

Attention-Deficit/Hyperactivity Disorder impacts children’s participation in activities that require attention to instruction, sustained mental effort, and executive functioning. Physical activity has been correlated to improvement in attention in children with ADHD. Rock climbing challenges muscular endurance, attention, and route planning. Five participants, aged 8-13, participated in the climbing program. Attention was measured pre and post climbing intervention with Trail Making Test B (TMT-B) for time to complete. Exercise intensity was measured by heart rate. Parent feedback on behavior was collected with the Conner’s Parent Rating Scale (CPRS). The social validity of the intervention was measured by the IRP-15 measures. Statistically, significant intrasession attention improvements were noted in all 5 climbers (p=.43). Two climbers were consistently working at a moderate intensity (40-60% HRmax) while 3 climbers maintained a light level of intensity (20-40% HRmax). No statistically significant improvements were found on the CPRS, although improvements are noted with qualitative reports from parents. The IRP-15 showed 100% of parents believed rock climbing was an effective intervention for their children with ADHD. Rock climbing at a light to moderate intensity is associated with improvements in attention and behavior in children with ADHD

General Static Solutions of 2-dimensional Einstein-Dilaton-Maxwell-Scalar Theories

General static solutions of effectively 2-dimensional Einstein-Dilaton-Maxwell-Scalar theories are obtained. Our model action includes a class of 2-d dilaton gravity theories coupled with a $U(1)$ gauge field and a massless scalar field. Therefore it also describes the spherically symmetric reduction of $d$-dimensional Einstein-Scalar-Maxwell theories. The properties of the analytic solutions are briefly discussed.Comment: 16 pages, Latex fil

A novel compartment, the 'subqpical stem' of the aerial hyphae, is the location of a sigN-dependent, developmentally distinct transcription in Streptomyces coelicolor.

Streptomyces coelicolor has nine SigB-like RNA polymerase sigma factors, several of them implicated in morphological differentiation and/or responses to different stresses. One of the nine, SigN, is the focus of this article. A constructed sigN null mutant was delayed in development and exhibited a bald phenotype when grown on minimal medium containing glucose as carbon source. One of two distinct sigN promoters, sigNP1, was active only during growth on solid medium, when its activation coincided with aerial hyphae formation. Transcription from sigNP1 was readily detected in several whi mutants (interrupted in morphogenesis of aerial mycelium into spores), but was absent from all bld mutants tested, suggesting that sigNP1 activity was restricted to the aerial hyphae. It also depended on sigN, thus sigN was autoregulated. Mutational and transcription studies revealed no functional significance to the location of sigN next to sigF, encoding another SigB-like sigma factor. We identified another potential SigN target, nepA, encoding a putative small secreted protein. Transcription of nepA originated from a single, aerial hyphae-specific and sigN-dependent promoter. While in vitro run-off transcription using purified SigN on the Bacillus subtilis ctc promoter confirmed that SigN is an RNA polymerase sigma factor, SigN failed to initiate transcription from sigNP1 and from the nepA promoter in vitro. Additional in vivo data indicated that further nepA upstream sequences, which are likely to bind a potential activator, are required for successful transcription. Using a nepA–egfp transcriptional fusion we located nepA transcription to a novel compartment, the ‘subapical stem’ of the aerial hyphae. We suggest that this newly recognized compartment defines an interface between the aerial and vegetative parts of the Streptomyces colony and might also be involved in communication between these two compartments

Plasma Wave Properties of the Schwarzschild Magnetosphere in a Veselago Medium

We re-formulate the 3+1 GRMHD equations for the Schwarzschild black hole in a Veselago medium. Linear perturbation in rotating (non-magnetized and magnetized) plasma is introduced and their Fourier analysis is considered. We discuss wave properties with the help of wave vector, refractive index and change in refractive index in the form of graphs. It is concluded that some waves move away from the event horizon in this unusual medium. We conclude that for the rotating non-magnetized plasma, our results confirm the presence of Veselago medium while the rotating magnetized plasma does not provide any evidence for this medium.Comment: 20 pages, 15 figures, accepted for publication in Astrophys. Space Sc

The emergence of the cortisol circadian rhythm in monozygotic and dizygotic twin infants: the twin-pair synchrony

OBJECTIVE: Studies on the influence of genetic factors on the ontogeny of cortisol circadian rhythm in infants are lacking. This study evaluated the influence of twinning and the heritability on the age of emergence of salivary cortisol rhythm. DESIGN AND SUBJECTS: A longitudinal study was performed using salivary samples obtained during morning and night, at 2, 4, 8, 12, 16, 20 and 24 weeks of postnatal life in 34 infants, 10 monozygotic (MZ) and 7 dizygotic (DZ) twin pairs. Salivary cortisol was determined by radioimmunoassay (RIA). Zigosity was verified by DNA analysis of at least 13 short tandem repeat polymorphisms. Difference of the emergence of cortisol circadian rhythm, within each twin pair, the intraclass correlation coefficient and the heritability index (h(2)) were calculated. RESULTS: The mean (± SEM) age of emergence of salivary cortisol circadian rhythm was similar in MZ and DZ (7·8 ± 1·0 vs 7·4 ± 1·3 weeks). Seven pairs showed coincidence of the emergence of cortisol rhythm. Ten pairs were not coincident; among them the within-pair difference of emergence of salivary circadian rhythm was similar in both MZ and DZ groups. The intraclass correlation coefficients were rMZ = 0·60, P = 0·02; and rDZ = 0·65, P = 0·03, respectively. The heritability index (h(2)) was 0·21 (ns). CONCLUSIONS: Salivary circadian rhythm appeared at the same postnatal age in MZ and DZ twin infants. Although several physiological aspects might be involved, the heritability index, obtained in the present study, suggests less genetic than environmental impact on the age of the onset of the cortisol circadian rhythm. Our data also indicated that each twin-pair show synchrony because they probably shared prenatal and postnatal environmental synchronizers