Differential bud activation by a net positive root signal explains branching phenotype in prostrate clonal herbs: a model.

Regulation of branching within perennial prostrate clonal herbs differs from the annual orthotropic species, Arabidopsis and pea, as the dominant signal transported from roots is a branching promoter, not an inhibitor. Trifolium repens, an exemplar of such prostrate species, was used to investigate the interaction between roots and branch development. This study tests whether or not current knowledge when synthesized into a predictive model is sufficient to simulate the branching pattern developing on the shoot distal to a basal root. The major concepts underpinning the model are: (i) bud outgrowth (activation) is stimulated in a dose-dependent manner by branching promoter signals from roots, (ii) the distribution of this net root stimulus (NRS) is uniform throughout the shoot system distal to the basal root but declines geometrically in intensity upon continued enlargement of this shoot system, and (iii) each bud has an outgrowth potential, equal to the activation level of the apical bud in which it forms, that moderates its response to NRS. The validity of these concepts was further tested by running simulations of the branching of a phylogenetically-distanced prostrate perennial monocotyledonous species, Tradescantia fluminensis. For both species the model reasonably accounted for the observed pattern of branching. The outgrowth potential of buds plays an important role in limiting the number of hierarchies of branching that can develop on a plant. In conclusion, for both species, the model accounted for the major factors involved in the correlative regulation of branching and is possibly also pertinent for all prostrate clonal species.

Measurement of fast neutron induced (n,γ) reaction cross-section of 68Zn, 96Zr, 121Sb and 123Sb in the energy range of 1 to 2 MeV.

The (n,γ) reaction cross-section for the elements 68Zn, 96Zr, 121Sb and 123Sb, present in the reactor structural/shielding materials, was measured by neutron activation technique in the neutron energy region of 1-2 MeV as very limited data is available in this energy range. Further, the neutron spectrum peaks in this energy region for the fast breeder reactors and proposed accelerator driven sub-critical systems. The natural strontium (natSr) element was used as a neutron flux monitor by considering effective combined reaction cross-section for 86Sr(n,γ)87Srm and 87Sr(n,n')87Srm reactions. The pellets of mixture of sample and monitor were irradiated by a quasi-mono energetic fast neutron beam, generated by 7Li(p,n)7Be reaction at FOTIA, Bhabha Atomic Research Centre, Mumbai, India. The activity of activation products was measured by off-line gamma-ray spectrometry using High Purity Germanium Detector (HPGe). The present data with improved uncertainty and covariance analysis enhance the cross-section data base for better constraining the evaluated data and theoretical models. The theoretical (n,γ) reaction cross-sections were calculated using TALYS 1.96, which could reasonably explain the present data with the Fermi gas level density prescription.

Preclinical trials in autosomal dominant AD: implementation of the DIAN-TU trial.

The Dominantly Inherited Alzheimer's Network Trials Unit (DIAN-TU) was formed to direct the design and management of interventional therapeutic trials of international DIAN and autosomal dominant Alzheimer's disease (ADAD) participants. The goal of the DIAN-TU is to implement safe trials that have the highest likelihood of success while advancing scientific understanding of these diseases and clinical effects of proposed therapies. The DIAN-TU has launched a trial design that leverages the existing infrastructure of the ongoing DIAN observational study, takes advantage of a variety of drug targets, incorporates the latest results of biomarker and cognitive data collected during the observational study, and implements biomarkers measuring Alzheimer's disease (AD) biological processes to improve the efficiency of trial design. The DIAN-TU trial design is unique due to the sophisticated design of multiple drugs, multiple pharmaceutical partners, academics servings as sponsor, geographic distribution of a rare population and intensive safety and biomarker assessments. The implementation of the operational aspects such as home health research delivery, safety magnetic resonance imagings (MRIs) at remote locations, monitoring clinical and cognitive measures, and regulatory management involving multiple pharmaceutical sponsors of the complex DIAN-TU trial are described.

A grid overlay framework for analysis of medical images and its application to the measurement of stroke lesions.

OBJECTIVES: To create and evaluate an interactive software tool for measuring imaging data in situations where hand-drawn region-of-interest measurements are unfeasible, for example, when the structure of interest is patchy with ill-defined boundaries. METHODS: An interactive grid overlay software tool was implemented that enabled coding of voxels dependent on their imaging appearance with a series of user-defined classes. The Grid Analysis Tool (GAT) was designed to automatically extract quantitative imaging data, grouping the results by tissue class. Inter- and intra-observer reproducibility was evaluated by six observers of various backgrounds in a study of acute stroke patients. RESULTS: The software tool enabled a more detailed classification of the stroke lesion than would be possible with a region-of-interest approach. However, inter-observer coefficients of variation (CVs) were relatively high, reaching 70% in "possibly abnormal" tissue and around 15-20% in normal appearing tissues, while intra-observer CVs were no more than 13% in "possibly abnormal" tissue and generally less than 1% in normal-appearing tissues. CONCLUSIONS: The grid-overlay method overcomes some of the limitations of conventional Region Of Interest (ROI) approaches, providing a viable alternative for segmenting patchy lesions with ill-defined boundaries, but care is required to ensure acceptable reproducibility if the method is applied by multiple observers. KEY POINTS: Computer software developed to overcome limitations of conventional regions of interest measurements • This software is suitable for patchy lesions with ill-defined borders • Allows a more detailed assessment of imaging data.

Existing branches correlatively inhibit further branching in Trifolium repens: possible mechanisms.

In Trifolium repens removal of any number of existing branches distal to a nodal root stimulates development of axillary buds further along the stem such that the complement of branches distal to a nodal root remains constant. This study aimed to assess possible mechanisms by which existing branches correlatively inhibit the outgrowth of axillary buds distal to them. Treatments were applied to basal branches to evaluate the roles of three postulated inhibitory mechanisms: (I) the transport of a phloem-mobile inhibitory feedback signal from branches into the main stem; (II) the polar flow of auxin from branches into the main stem acting to limit further branch development; or (III) the basal branches functioning as sinks for a net root-derived stimulatory signal (NRS). Results showed that transport of auxin, or of a non-auxin phloem-mobile signal, from basal branches did not influence regulation of correlative inhibition and were consistent with the possibility that the intra-plant distribution of NRS could be involved in the correlative inhibition of distal buds by basal branches. This study supports existing evidence that regulation of branching in T. repens is dominated by a root-derived stimulatory signal, initially distributed via the xylem, the characterization of which will progress the generic understanding of branching regulation.

Predominant time scales in fission processes in reactions of S, Ti and Ni with W: zeptosecond versus attosecond.

The inhibition of fusion by quasifission is crucial in limiting the formation of superheavy elements in collisions of heavy nuclei. Time scales of ∼10(-18) s inferred for fissionlike events from recent crystal blocking measurements were interpreted to show either that quasifission itself is slower than previously believed, or that the fraction of slow fusion-fission is higher than expected. New measurements of mass-angle distributions for (48)Ti and (64)Ni bombarding W targets show that in these reactions quasifission is the dominant process, typically occurring before the system formed after contact has made a single rotation, corresponding to time scales of ≤10(-20) s.

Low energy proton beam induces efficient cell killing in A549 lung adenocarcinoma cells.

The aim of the current study was to determine the signaling differences between gamma- and proton beam-irradiations. A549 lung adenocarcinoma cells were irradiated with 2 Gy proton beam or gamma-radiation. Proton beam was found to be more cytotoxic than gamma-radiation. Proton beam-irradiated cells showed phosphorylation of H2AX, ATM, Chk2, and p53. The mechanism of excessive cell killing in proton beam-irradiated cells was found to be upregulation of Bax and downregulation of Bcl-2. The noteworthy finding of this study is the biphasic activation of the sensor proteins, ATM, and DNA-PK and no activation of ATR by proton irradiation.

Axillary bud outgrowth potential is determined by parent apical bud activity.

Axillary buds within a plant shoot system are known to differ in their ability to respond to treatments favouring their development. This ability is referred to as their outgrowth potential. Using two species of prostrate nodally-rooting herbs, dicotyledonous Trifolium repens and monocotyledonous Tradescantia fluminensis, grown throughout in a strictly vegetative state, this study tested two hypotheses. Hypothesis 1: that each axillary bud exhibits an outgrowth potential that is directly related to the growth rate of its parent apical bud, and Hypothesis 2: that the growth rate attained by an axillary bud depends upon both its outgrowth potential and the local supply of stimulatory root-derived signal (NRS) available to it. Activation levels (growth rates) of apical buds were varied by differential exposure to nodal roots and the outgrowth responses of axillary buds recently emerged from them were then measured under standardized conditions of NRS supply. Hypothesis 1 was shown to be correct for both species. Hypothesis 2, tested only in T. repens, was supported by results showing that an axillary bud's outgrowth potential and the NRS supply to it each independently influenced its growth rate, there being no significant interaction between the two. These results emphasize the significant role the physiological state/activity of apical buds has on the outgrowth potential of axillary buds formed within them. The fact that similar relationships were observed on axillary buds on stems of differing developmental maturity and branching hierarchy, and in two taxonomically diverse species, suggests they might be widespread among morphologically similar species.

Regulation of shoot branching patterns by the basal root system: towards a predictive model.

This study aimed to underpin the development of a generic predictive model of the regulation of shoot branching by roots in nodally rooting perennial prostrate-stemmed species using knowledge gained from physiological studies of Trifolium repens. Experiment 1 demonstrated that the net stimulatory influence from the basal rooted region of the plant on growth of newly emerging axillary buds on the primary stem decreased as their phytomeric distance from the basal root system increased. Experiment 2 found that at any one time the distribution of net root stimulus (NRS) to the apical bud on the primary stem and all lateral branches was fairly uniform within a single plant. Thus, although NRS availability was uniform throughout the shoot system at any point in time, it progressively decreased as shoot apical buds grew away from the basal root system. Based on these findings, a preliminary predictive model of the physiological regulation of branching pattern was developed. This model can explain the decline in growth rate of buds on a primary stem as it grows away from its basal root system but not the rapid progressive decline in secondary branch development on successive lateral branches. Thus knowledge of NRS availability to emerging buds is not, by itself, a sufficient basis from which to construct a predictive model. In addition, it seems that the ability of an emerging bud to become activated in response to its local NRS availability is, at least in part, directly influenced by the activation level of its parent apical bud. The experimental testing of this hypothesis, required for continued development of the model, is proceeding.

Do patients with p16-positive oropharyngeal squamous cell carcinoma get more bone metastasis than p16-negative patients?

BACKGROUND: Oropharyngeal squamous cell carcinoma is thought to rarely metastasise to bone. This study hypothesised that in p16-positive disease there is a significant incidence of bony metastasis. METHODS: This was an ambispective cohort review. All patients with oropharyngeal squamous cell carcinoma diagnosed and treated at one centre were included. RESULTS: A total of 180 consecutive patients were identified over 5 years. Fifteen patients were excluded because of lack of p16 status, none of whom had bony metastasis. The final analysis included 165 patients: 48 (29.09 per cent) in the p16-negative group and 117 (70.91 per cent) in the p16-positive group. Ten patients (8.55 per cent) in the p16-positive group developed bony metastasis, compared with zero in the p16-negative group; this difference was statistically significant (p = 0.036). CONCLUSION: Expression of p16 was associated with an increased incidence in bony metastasis in this cohort. This is the first study to explore this specific question.