Estimates of free and bound indole-3-acetic acid and zeatin levels in relation to regulation of apical dominance and tiller release in oat shoots

Oat stem segments containing quiescent lateral (tiller) buds during times of strong apical dominance, and growing buds released from this inhibition, were collected for analysis of native auxin and cytokinins. Free IAA and IAA conjugates were determined by a 14 C-IAA and 14 C-IBA double isotope dilution assay. Free zeatin (Z), zeatin riboside (Z-r), and their glucoside conjugates were purified from butanol-soluble fractions by means of a cellulose phosphate exchanger and thin-layer chromatography. Hormones were analyzed by gas chromatography and mass spectrometry (GC-MS). Results of these analyses indicate that changes in free and bound IAA within the stem do not correlate well with the release of tiller buds (as brought about by decapitation, gravistimulation, or the emergence of the inflorescence). However, increases in Z-r levels are well correlated with tiller release. The glucoside conjugate of Z-r may act as a storage form of cytokinin in quiescent tiller buds. In light of these results, we find that the auxin-cytokinin ratio in oat stem segments is shifted during tillerPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45928/1/344_2005_Article_BF02042250.pd

Hierarchical Control Implementation for Meshed AC/Multi-terminal DC Grids with Offshore Windfarms Integration

Although the integration of meshed multi-terminal direct current (MTDC) grids with the existing AC grid has some added economic advantages, significant challenges are encountered in such systems. One of the major challenges is ensuring secure and optimal operation of the combined AC/MTDC grid considering the stability requirements of AC and DC grids at different operating conditions. This paper presents the implementation of hierarchical control for the combined AC/MTDC grid. The hierarchical control is based on the well-established three-layered control of the AC power system, comprising primary, secondary, and tertiary controls. A set of appropriate control methods are proposed for the primary, secondary, and tertiary control layers to accomplish the identified requirements for secure and optimal operation of the combined AC/MTDC grid

Truncated and Helix-Constrained Peptides with High Affinity and Specificity for the cFos Coiled-Coil of AP-1

Protein-based therapeutics feature large interacting surfaces. Protein folding endows structural stability to localised surface epitopes, imparting high affinity and target specificity upon interactions with binding partners. However, short synthetic peptides with sequences corresponding to such protein epitopes are unstructured in water and promiscuously bind to proteins with low affinity and specificity. Here we combine structural stability and target specificity of proteins, with low cost and rapid synthesis of small molecules, towards meeting the significant challenge of binding coiled coil proteins in transcriptional regulation. By iteratively truncating a Jun-based peptide from 37 to 22 residues, strategically incorporating i-->i+4 helix-inducing constraints, and positioning unnatural amino acids, we have produced short, water-stable, alpha-helical peptides that bind cFos. A three-dimensional NMR-derived structure for one peptide (24) confirmed a highly stable alpha-helix which was resistant to proteolytic degradation in serum. These short structured peptides are entropically pre-organized for binding with high affinity and specificity to cFos, a key component of the oncogenic transcriptional regulator Activator Protein-1 (AP-1). They competitively antagonized the cJun–cFos coiled-coil interaction. Truncating a Jun-based peptide from 37 to 22 residues decreased the binding enthalpy for cJun by ~9 kcal/mol, but this was compensated by increased conformational entropy (TDS ≤ 7.5 kcal/mol). This study demonstrates that rational design of short peptides constrained by alpha-helical cyclic pentapeptide modules is able to retain parental high helicity, as well as high affinity and specificity for cFos. These are important steps towards small antagonists of the cJun-cFos interaction that mediates gene transcription in cancer and inflammatory diseases

Evaluation of machine-learning methods for ligand-based virtual screening

Machine-learning methods can be used for virtual screening by analysing the structural characteristics of molecules of known (in)activity, and we here discuss the use of kernel discrimination and naive Bayesian classifier (NBC) methods for this purpose. We report a kernel method that allows the processing of molecules represented by binary, integer and real-valued descriptors, and show that it is little different in screening performance from a previously described kernel that had been developed specifically for the analysis of binary fingerprint representations of molecular structure. We then evaluate the performance of an NBC when the training-set contains only a very few active molecules. In such cases, a simpler approach based on group fusion would appear to provide superior screening performance, especially when structurally heterogeneous datasets are to be processed

The World Trade Center Disaster and the Health of Workers: Five-Year Assessment of a Unique Medical Screening Program

BACKGROUND: Approximately 40,000 rescue and recovery workers were exposed to caustic dust and toxic pollutants following the 11 September 2001 attacks on the World Trade Center (WTC). These workers included traditional first responders, such as firefighters and police, and a diverse population of construction, utility, and public sector workers. METHODS: To characterize WTC-related health effects, the WTC Worker and Volunteer Medical Screening Program was established. This multicenter clinical program provides free standardized examinations to responders. Examinations include medical, mental health, and exposure assessment questionnaires; physical examinations; spirometry; and chest X rays. RESULTS: Of 9,442 responders examined between July 2002 and April 2004, 69% reported new or worsened respiratory symptoms while performing WTC work. Symptoms persisted to the time of examination in 59% of these workers. Among those who had been asymptomatic before September 11, 61% developed respiratory symptoms while performing WTC work. Twenty-eight percent had abnormal spirometry; forced vital capacity (FVC) was low in 21%; and obstruction was present in 5%. Among nonsmokers, 27% had abnormal spirometry compared with 13% in the general U.S. population. Prevalence of low FVC among nonsmokers was 5-fold greater than in the U.S. population (20% vs. 4%). Respiratory symptoms and spirometry abnormalities were significantly associated with early arrival at the site. CONCLUSION: WTC responders had exposure-related increases in respiratory symptoms and pulmonary function test abnormalities that persisted up to 2.5 years after the attacks. Long-term medical monitoring is required to track persistence of these abnormalities and identify late effects, including possible malignancies. Lessons learned should guide future responses to civil disasters

Testing the cognitive-behavioural maintenance models across DSM-5 bulimic-type eating disorder diagnostic groups: A multi-centre study

The original cognitive-behavioural (CB) model of bulimia nervosa, which provided the basis for the widely used CB therapy, proposed that specific dysfunctional cognitions and behaviours maintain the disorder. However, amongst treatment completers, only 40–50 % have a full and lasting response. The enhanced CB model (CB-E), upon which the enhanced version of the CB treatment was based, extended the original approach by including four additional maintenance factors. This study evaluated and compared both CB models in a large clinical treatment seeking sample (N = 679), applying both DSM-IV and DSM-5 criteria for bulimic-type eating disorders. Application of the DSM-5 criteria reduced the number of cases of DSM-IV bulimic-type eating disorders not otherwise specified to 29.6 %. Structural equation modelling analysis indicated that (a) although both models provided a good fit to the data, the CB-E model accounted for a greater proportion of variance in eating-disordered behaviours than the original one, (b) interpersonal problems, clinical perfectionism and low self-esteem were indirectly associated with dietary restraint through over-evaluation of shape and weight, (c) interpersonal problems and mood intolerance were directly linked to binge eating, whereas restraint only indirectly affected binge eating through mood intolerance, suggesting that factors other than restraint may play a more critical role in the maintenance of binge eating. In terms of strength of the associations, differences across DSM-5 bulimic-type eating disorder diagnostic groups were not observed. The results are discussed with reference to theory and research, including neurobiological findings and recent hypotheses

Human skin penetration of a copper tripeptide in vitro as a function of skin layer

Objective and designSkin retention and penetration by copper applied as glycyl-L-histidyl-L-lysine cuprate diacetate was evaluated in vitro in order to assess its potential for its transdermal delivery as an anti-inflammatory agent.Materials and methodsFlow-through diffusion cells with 1 cm(2) exposure area were used under infinite dose conditions. 0.68% aq. copper tripeptide as permeant was applied on isolated stratum corneum, heat-separated epidermis and dermatomed skin and receptor fluid collected over 48 h in 4 h intervals using inductively coupled plasma mass spectrometry to analyze for copper in tissues and receptor fluid.ResultsThe permeability coefficient of the compound through dermatomed skin was 2.43 ± 0.51 × 10(-4) cm/h; 136.2 ± 17.5 μg/cm(2) copper permeated 1 cm(2) of that tissue over 48 h, while 97 ± 6.6 μg/cm(2) were retained as depot.ConclusionsCopper as tripeptide was delivered in potentially therapeutically effective amounts for inflammatory disease

Human skin penetration of a copper tripeptide in vitro as a function of skin layer

We study a set of 28 GRB light-curves detected between 15 December 2002 and 9 June 2003 by the anti-coincidence shield of the spectrometer (SPI) of INTEGRAL. During this period it has detected 50 bursts, that have been confirmed by other instruments, with a time resolution of 50 ms. First, we derive the basic characteristics of the bursts: various duration measures, the count peak flux and the count fluence. Second, a sub-sample of 11 bursts with 12 individual, well-separated pulses is studied. We fit the pulse shape with a model by Kocevski et al. (2003) and find that the pulses are quite self-similar in shape. There is also a weak tendency for the pulses with steep power-law decays to be more asymmetric. Third, the variability of the complex light-curves is studied by analyzing their power-density-spectra (PDS) and their RMS variability.
The averaged PDS, of the whole sample, is a power-law with index of $1.60\pm0.05$ and a break between 1–2 Hz. Fourth, we also discuss the background and noise levels. We found that the background noise has a Gaussian distribution and its power is independent of frequency, i.e., it is white noise. However, it does not follow a Poisson statistic since on average the variance is ~1.6 larger than the mean. We discuss our results in context of the current theoretical picture in which GRBs are created in an anisotropic, highly relativistic outflow from collapsing massive stars. Finally, we note that the exact behaviour of the instrument is not yet known and therefore the above results should be treated as preliminary.