A 22-nt artificial microRNA mediates widespread RNA silencing in Arabidopsis

It is known that 22-nucleotide (nt) microRNAs (miRNAs) derived from asymmetric duplexes trigger phased small-interfering RNA (phasiRNA) production from complementary targets. Here we investigate the efficacy of 22-nt artificial miRNA (amiRNA)-mediated RNA silencing relative to conventional hairpin RNA (hpRNA) and 21-nt amiRNA-mediated RNA silencing. CHALCONE SYNTHASE (CHS) was selected as a target in Arabidopsis thaliana due to the obvious and non-lethal loss of anthocyanin accumulation upon widespread RNA silencing. Over-expression of CHS in the pap1-D background facilitated visual detection of both local and systemic RNA silencing. RNA silencing was initiated in leaf tissues from hpRNA and amiRNA plant expression vectors under the control of an Arabidopsis RuBisCo small subunit 1A promoter (SSU). In this system, hpRNA expression triggered CHS silencing in most leaf tissues but not in roots or seed coats. Similarly, 21-nt amiRNA expression from symmetric miRNA/miRNA* duplexes triggered CHS silencing in all leaf tissues but not in roots or seed coats. However, 22-nt amiRNA expression from an asymmetric duplex triggered CHS silencing in all tissues, including roots and seed coats, in the majority of plant lines. This widespread CHS silencing required RNA-DEPENDENT RNA POLYMERASE6-mediated accumulation of phasiRNAs from the endogenous CHS transcript. These results demonstrate the efficacy of asymmetric 22-nt amiRNA-directed RNA silencing and associated phasiRNA production and activity, in mediating widespread RNA silencing of an endogenous target gene. Asymmetric 22-nt amiRNA-directed RNA silencing requires little modification of existing amiRNA technology and is expected to be effective in suppressing other genes and/or members of gene families.

Hearing loss and a supportive tactile signal in a navigation system : effects on driving behavior and eye movements

An on-road study was conducted to evaluate a complementary tactile navigation signal on driving behaviour and eye movements for drivers with hearing loss (HL) compared to drivers with normal hearing (NH). 32 participants (16 HL and 16 NH) performed two preprogrammed navigation tasks. In one, participants received only visual information, while the other also included a vibration in the seat to guide them in the correct direction. SMI glasses were used for eye tracking, recording the point of gaze within the scene. Analysis was performed on predefined regions. A questionnaire examined participant's experience of the navigation systems. Hearing loss was associated with lower speed, higher satisfaction with the tactile signal and more glances in the rear view mirror. Additionally, tactile support led to less time spent viewing the navigation display.

Resistance to exercise-induced weight loss : compensatory behavioral adaptations

In many interventions that are based on an exercise program intended to induce weight loss, the mean weight loss observed is modest and sometimes far less than what the individual expected. The individual responses are also widely variable, with some individuals losing a substantial amount of weight, others maintaining weight, and a few actually gaining weight. The media have focused on the subpopulation that loses little weight, contributing to a public perception that exercise has limited utility to cause weight loss. The purpose of the symposium was to present recent, novel data that help explain how compensatory behaviors contribute to a wide discrepancy in exercise-induced weight loss. The presentations provide evidence that some individuals adopt compensatory behaviors, that is, increased energy intake and/or reduced activity, that offset the exercise energy expenditure and limit weight loss. The challenge for both scientists and clinicians is to develop effective tools to identify which individuals are susceptible to such behaviors and to develop strategies to minimize their effect.

The adaptive metabolic response to exercise-induced weight loss influences both energy expenditure and energy intake

BACKGROUND/OBJECTIVEs A decline in resting energy expenditure (REE) beyond that predicted from changes in body composition has been noted following dietary-induced weight loss. However, it is unknown whether a compensatory downregulation in REE also accompanies exercise (EX)-induced weight loss, or whether this adaptive metabolic response influences energy intake (EI). SUBJECTS/METHODS Thirty overweight and obese women (body mass index (BMI)=30.6±3.6 kg/m2) completed 12 weeks of supervised aerobic EX. Body composition, metabolism, EI and metabolic-related hormones were measured at baseline, week 6 and post intervention. The metabolic adaptation (MA), that is, difference between predicted and measured REE was also calculated post intervention (MApost), with REE predicted using a regression equation generated in an independent sample of 66 overweight and obese women (BMI=31.0±3.9 kg/m2). RESULTS Although mean predicted and measured REE did not differ post intervention, 43% of participants experienced a greater-than-expected decline in REE (−102.9±77.5 kcal per day). MApost was associated with the change in leptin (r=0.47; P=0.04), and the change in resting fat (r=0.52; P=0.01) and carbohydrate oxidation (r=−0.44; P=0.02). Furthermore, MApost was also associated with the change in EI following EX (r=−0.44; P=0.01). CONCLUSIONS Marked variability existed in the adaptive metabolic response to EX. Importantly, those who experienced a downregulation in REE also experienced an upregulation in EI, indicating that the adaptive metabolic response to EX influences both physiological and behavioural components of energy balance.

Vulnerability held not to be pre-requisite for establishing a duty of care in claims of pure economic Loss

Case note Apache Energy Ltd v Alcoa of Australia Ltd (No 2) [2013] In 2011, headlines were made when Alcoa sued Apache Energy and its partners for $158 million, a loss it claimed was a consequence of Apache Energy failing to adequately inspect and maintain the gas pipelines that supplied the gas used by Alcoa in its business. As the loss was not a consequence of any property damage or injury to Alcoa, the loss is characterised as pure economic loss...

Loss reduction experiences in electric power distribution companies of Iran

The experiences of the loss reduction projects in electric power distribution companies (EPDCs) of Iran are presented. The loss reduction methods, which are proposed individually by 14 EPDCs, corresponding energy saving (ES), Investment costs (IC), and loss rate reductions are provided. In order to illustrate the effectiveness and performance of the loss reduction methods, three parameters are proposed as energy saving per investment costs (ESIC), energy saving per quantity (ESPQ), and investment costs per quantity (ICPQ). The overall ESIC of 14 EPDC as well as individual average and standard deviation of the EISC for each method is presented and compared. In addition, the average and standard deviation of the ESPQs and ICPQs for the loss reduction methods, individually, are provided and investigated. These parameters are useful for EPDCs that intend to reduce the electric losses in distribution networks as a benchmark and as a background in the planning purposes.

Loss reduction planning in electric distribution networks of IRAN until 2025

In this paper, a loss reduction planning in electric distribution networks is presented based on the successful experiences in distribution utilities of IRAN and some developed countries. The necessary technical and economical parameters of planning are calculated from related projects in IRAN. Cost, time, and benefits of every sub-program including seven loss reduction approaches are determined. Finally, the loss reduction program, the benefit per cost, and the return of investment in optimistic and pessimistic conditions are introduced.

Distribution feeder reconfiguration for loss minimization based on modified honey bee mating optimization algorithm

This paper presents an efficient algorithm for multi-objective distribution feeder reconfiguration based on Modified Honey Bee Mating Optimization (MHBMO) approach. The main objective of the Distribution feeder reconfiguration (DFR) is to minimize the real power loss, deviation of the nodes’ voltage. Because of the fact that the objectives are different and no commensurable, it is difficult to solve the problem by conventional approaches that may optimize a single objective. So the metahuristic algorithm has been applied to this problem. This paper describes the full algorithm to Objective functions paid, The results of simulations on a 32 bus distribution system is given and shown high accuracy and optimize the proposed algorithm in power loss minimization.

Kamouflage : loss-resistant password management

We introduce Kamouflage: a new architecture for building theft-resistant password managers. An attacker who steals a laptop or cell phone with a Kamouflage-based password manager is forced to carry out a considerable amount of online work before obtaining any user credentials. We implemented our proposal as a replacement for the built-in Firefox password manager, and provide performance measurements and the results from experiments with large real-world password sets to evaluate the feasibility and effectiveness of our approach. Kamouflage is well suited to become a standard architecture for password managers on mobile devices.

Loss of chromosomal integrity in human mammary epithelial cells subsequent to escape from senescence

The genomic changes that foster cancer can be either genetic or epigenetic in nature. Early studies focused on genetic changes and how mutational events contribute to changes in gene expression. These point mutations, deletions and amplifications are known to activate oncogenes and inactivate tumor suppressor genes. More recently, multiple epigenetic changes that can have a profound effect on carcinogenesis have been identified. These epigenetic events, such as the methylation of promoter sequences in genes, are under active investigation. In this review we will describe a methylation event that occurs during the propagation of human mammary epithelial cells (HMEC) in culture and detail the accompanying genetic alterations that have been observed.

The collision induced loss of carbon monoxide from deprotonated benzyl benzoate in the gas phase. An anionic 1,2-Wittig type rearrangement

The ion PhCO2--CHPh, upon collision activation, undergoes competitive losses of CO and CO2 of which the former process produces the base peak of the spectrum. Product ion and substituent effect (Hammett) studies indicate that PhCO2--CHPh cyclises to a deprotonated hydroxydiphenyloxirane which ring opens to PhCOCH(O-)Ph. This anion then undergoes an anionic 1,2-Wittig type rearrangement {through [PhCO- (PhCHO)]} to form Ph2CHO- and CO. The mechanism of the 1,2-rearrangement has been probed by an ab initio study [at MP4(SDTQ)/6-31++G(d,p) level] of the model system HCOCH2O- →; MeO- + CO The analogous system RCO2--CHPh (R = alkyl) similarly loses CO, and the migratory aptitudes of the alkyl R groups in this reaction are Bu′ > Me > Et ∼Pri). This trend correlates with the order of anion basicities (i.e. the order of ΔG○acid values of RH), supporting the operation of an anion migration process. The loss of CO2 from PhCO2--CHPh yields Ph2CH- as the anionic product: several mechanistic scenarios are possible, one of which involves an initial ipso nucleophilic substitution.

The loss of CO from the ortho, meta and para forms of deprotonated methyl benzoate in the gas phase

The ortho, meta and para anions of methyl benzoate may be made in the source of a mass spectrometer by the S(N)2(Si) reactions between HO- and methyl (o-, m-, and p-trimethylsilyl)benzoate respectively. All three anions lose CO upon collisional activation to form the ortho anion of anisole in the ratio ortho>>meta > para. The rearrangement process is charge directed through the ortho anion. Theoretical calculations at the B3LYP/6-311++G(d,p)//HF/6-31+G(d) level of theory indicate that the conversion of the meta and para anions to the ortho anion prior to loss of CO involve 1,2-H transfer(s), rather than carbon scrambling of the methoxycarbonylphenyl anion. There are two mechanisms which can account for this rearrangement, viz. (A) cyclisation of the ortho anion centre to the carbonyl group of the ester to give a cyclic carbonyl system in which the incipient methoxide anion substitutes at one of the two equivalent ring carbons of the three membered ring to yield an intermediate which loses CO to give the ortho anion of anisole, and (B) an elimination reaction to give an intermediate benzyne-methoxycarbonyl anion complex in which the MeOCO- species acts as a MeO- donor, which then adds to benzyne to yield the ortho anion of anisole. Calculations at the B3LYP/6-311++G(d,p)//HF/6-31+G(d) level of theory indicate that (i) the barrier in the first step (the rate determining step) of process A is 87 kJ mol(-1) less than that for the synchronous benzyne process B, and (ii) there are more low frequency vibrations in the transition state for benzyne process B than for the corresponding transition state for process A. Stepwise process A has the lower barrier for the rate determining step, and the lower Arrhenius factor: we cannot differentiate between these two mechanisms on available evidence.

Loss of epithelial markers and acquisition of vimentin expression in adriamycin- and vinblastine-resistant human breast cancer cell lines

We have previously observed that breast cancer cell lines could exhibit either epithelial or fibroblastic phenotypes as reflected by their morphologies and intermediate filament protein expression (C. L. Sommers, D. Walker-Jones, S. E. Heckford, P. Worland, E. Valverius, R. Clark, M. Stampfer, and E. P. Gelmann, Cancer Res., 49: 4258-4263, 1989). Fibroblastoid, vimentin-expressing breast cancer cell lines are more invasive in vitro and in vivo (E. W. Thompson, S. Paik, N. Brunner, C. L. Sommers, G. Zugmaier, R. Clarke, T. B. Shima, J. Torri, S. Donahue, M. E. Lippman, G. R. Martin, and R. B. Dickson, J. Cell. Physiol., 150: 534-544, 1992). We hypothesized that a breast cancer cell with an epithelial phenotype could undergo a transition to a fibroblastic phenotype, possibly resulting in more invasive capacity. We now show that two Adriamycin-resistant MCF-7 cell lines and a vinblastine-resistant ZR-75-B cell line have undergone such a transition. Adriamycin-resistant MCF-7 cells express vimentin, have diminished keratin 19 expression, have lost cell adhesion molecule uvomorulin expression, and have reduced formation of desmosomes and tight junctions as determined by reduced immunodetection of their components desmoplakins I and II and zonula occludens (ZO)-1. Other MCF-7 cell lines selected for resistance to vinblastine and to Adriamycin and verapamil did not have these characteristics, indicating that drug selection does not invariably cause these phenotypic changes. In addition, to determine if vimentin expression in MCF-7 cells alone could manifest a fibroblastic phenotype, we transfected the full-length human vimentin complementary DNA into MCF-7 cells. Although vimentin expression was achieved in MCF-7 cells, it did not affect the phenotype of the cells in terms of the distribution of keratins, desmoplakins I and II, ZO-1, or uvomorulin or in terms of in vitro invasiveness. We conclude that vimentin expression is a marker for a fibroblastic and invasive phenotype in breast cancer cells but does not by itself give rise to this phenotype.