Mapping and controlling molecular processes: The application of control theory and system identification algorithms to ASOPS and other fast pulse spectroscopies

Asynchronous Optical Sampling (ASOPS) [1,2] and frequency comb spectrometry [3] based on dual Ti:saphire resonators operated in a master/slave mode have the potential to improve signal to noise ratio in THz transient and IR sperctrometry. The multimode Brownian oscillator time-domain response function described by state-space models is a mathematically robust framework that can be used to describe the dispersive phenomena governed by Lorentzian, Debye and Drude responses. In addition, the optical properties of an arbitrary medium can be expressed as a linear combination of simple multimode Brownian oscillator functions. The suitability of a range of signal processing schemes adopted from the Systems Identification and Control Theory community for further processing the recorded THz transients in the time or frequency domain will be outlined [4,5]. Since a femtosecond duration pulse is capable of persistent excitation of the medium within which it propagates, such approach is perfectly justifiable. Several de-noising routines based on system identification will be shown. Furthermore, specifically developed apodization structures will be discussed. These are necessary because due to dispersion issues, the time-domain background and sample interferograms are non-symmetrical [6-8]. These procedures can lead to a more precise estimation of the complex insertion loss function. The algorithms are applicable to femtosecond spectroscopies across the EM spectrum. Finally, a methodology for femtosecond pulse shaping using genetic algorithms aiming to map and control molecular relaxation processes will be mentioned.

Local roles of TGF-beta superfamily members in the control of ovarian follicle development

Members of the transforming growth factor-beta (TGF-beta) superfamily have wide-ranging influences on many tissue and organ systems including the ovary. Two recently discovered TGF-beta superfamily members, growth/differentiation factor-9 (GDF-9) and bone morphogenetic protein-15 (BMP-15; also designated as GDF-9B) are expressed in an oocyte-specific manner from a very early stage and play a key role in promoting follicle growth beyond the primary stage. Follicle growth to the small antral stage does not require gonadotrophins but appears to be driven by local autocrine/paracrine signals from both somatic cell types (granulosa and theca) and from the oocyte. TGF-beta superfamily members expressed by follicular cells and implicated in this phase of follicle development include TGF-beta, activin, GDF-9/9B and several BMPs. Acquisition of follicle-stimulating hormone (FSH) responsiveness is a pre-requisite for growth beyond the small antral stage and evidence indicates an autocrine role for granulosa-derived activin in promoting granulosa cell proliferation, FSH receptor expression and aromatase activity. Indeed, some of the effects of FSH on granulosa cells may be mediated by endogenous activin. At the same time, activin may act on theca cells to attenuate luteinizing hormone (LH)-dependent androgen production in small to medium-size antral follicles. Dominant follicle selection appears to depend on differential FSH sensitivity amongst a growing cohort of small antral follicles. Activin may contribute to this selection process by sensitizing those follicles with the highest "activin tone" to FSH. Production of inhibin, like oestradiol, increases in selected dominant follicles, in an FSH- and insulin-like growth factor-dependent manner and may exert a paracrine action on theca cells to upregulate LH-induced secretion of androgen, an essential requirement for further oestradiol secretion by the pre-ovulatory follicle. Like activin, BMP-4 and -7 (mostly from theca), and BMP-6 (mostly from oocyte), can enhance oestradiol and inhibin secretion by bovine granulosa cells while suppressing progesterone secretion; this suggests a functional role in delaying follicle luteinization and/or atresia. Follistatin, on the other hand, may favor luteinization and/or atresia by bio-neutralizing intrafollicular activin and BMPs. Activin receptors are expressed by the oocyte and activin may have a further intrafollicular role in the terminal stages of follicle differentiation to promote oocyte maturation and developmental competence. In a reciprocal manner, oocyte-derived GDF-9/9B may act on the surrounding cumulus granulosa cells to attenuate oestradiol output and promote progesterone and hyaluronic acid production, mucification and cumulus expansion.(C) 2003 Elsevier Science B.V. All rights reserved.

Improvement of link failure restoration utilising multi-protocol label switching (MPLS) as a means to maintain quality of service (QOS)

This paper proposes a practical approach to the enhancement of Quality of Service (QoS) routing by means of providing alternative or repair paths in the event of a breakage of a working path. The proposed scheme guarantees that every Protected Node (PN) is connected to a multi-repair path such that no further failure or breakage of single or double repair paths can cause any simultaneous loss of connectivity between an ingress node and an egress node. Links to be protected in an MPLS network are predefined and a Label Switched path (LSP) request involves the establishment of a working path. The use of multi-protection paths permits the formation of numerous protection paths allowing greater flexibility. Our analysis examined several methods including single, double and multi-repair routes and the prioritization of signals along the protected paths to improve the Quality of Service (QoS), throughput, reduce the cost of the protection path placement, delay, congestion and collision. Results obtained indicated that creating multi-repair paths and prioritizing packets reduces delay and increases throughput in which case the delays at the ingress/egress LSPs were low compared to when the signals had not been classified. Therefore the proposed scheme provided a means to improve the QoS in path restoration in MPLS using available network resources. Prioritizing the packets in the data plane has revealed that the amount of traffic transmitted using a medium and low priority Label Switch Paths (LSPs) does not have any impact on the explicit rate of the high priority LSP in which case the problem of a knock-on effect is eliminated.

Inheritance, access to resources and poverty in Serer families in Senegal

This research explores the relationship between inheritance, access to resources and the intergenerational transmission of poverty among the Serer ethnic group in rural and urban environments in Senegal. In many Sub-Saharan African countries, customary law excludes women from owning and inheriting assets, such as land and property. Yet, assets controlled by women often result in increased investments in the next generation's health, nutrition and schooling and reduce the intergenerational transmission of poverty. Qualitative research with 60 participants in Senegal reveals the important role that land, housing and financial assets may play in building resilience to household shocks and interrupting the intergenerational transmission of poverty. However, the protection afforded by these assets was often dependent on other factors, including human, social and environmental capital. The death of a spouse or parent had major emotional and material impacts on many Serer families. The inheritance and control of assets and resources was strongly differentiated among family members along lines of gender, age and generation. Younger widows and their children were particularly vulnerable to chronic poverty. Although inheritance disputes were rare, the research suggests they are more likely between co-wives in polygamous unions and their children, particularly in urban areas. In addition to experiencing economic and health-related shocks, many interviewees were exposed to a range of climate-related risks and environmental pressures which increased their vulnerability. Family members coped with these shocks and risks by diversifying livelihoods, migrating to urban areas and other regions for work, participating in women's co-operatives and associations and developing supportive social networks with extended family and community members. Policies and practices that may help to alleviate poverty, safeguard women's and young people's inheritance and build resilience to financial, health-related and environmental shocks and risks include: - Social protection measures targeted towards poor widows and orphaned children, such as social and cash transfers to pay for basic needs including food, healthcare and children's schooling. - Micro-finance initiatives and credit and savings schemes, alongside training and capacity-building targeted to women and young people to develop income-generation activities and skills. - Free legal advice, support and advocacy for women and young people to pursue inheritance claims through the legal system. - Raising awareness about women's and children's legal rights and working with government and community and religious leaders to tackle discriminatory inheritance practices and contradictions caused by legal pluralism. - Increasing women's control of land and access to inputs, enhancing their business, organisational, and leadership skills and promoting civic participation in local, regional and national decision-making processes. - Improving access to basic services in rural areas, particularly healthcare, building the quality of education and promoting girls' access to education - Enhancing agricultural production and providing more employment opportunities, apprenticeships and vocational training for young people, particularly in rural areas.

Lexical access, story re-telling and sequencing skills in adults who clutter and those who do not

Cluttering is a rate-based disorder of fluency, the scope of whose diagnostic criteria currently remains unclear. This paper reports preliminary findings from a larger study which aims to determine whether cluttering can be associated with language disturbances as well as motor and rate based ones. Subtests from the Mt Wilga High Level Language Test (MWHLLT) were used to determine whether people who clutter (PWC) have word finding difficulties, and use significantly more maze behaviours compared to controls, during story re-telling and simple sequencing tasks. Independent t tests showed that PWC were significantly slower than control participants in lexical access and sentence completion tasks, but returned mixed findings when PWCs were required to name items within a semantic category. PWC produced significantly more maze behaviour than controls in a task where participants were required to explain how to undertake commonly performed actions, but no difference in use of maze behaviour was found between the two groups when retelling a story from memory. The implications of these findings are discussed

Robotic multiwell planar patch-clamp for native and primary mammalian cells

Robotic multiwell planar patch-clamp has become common in drug development and safety programs because it enables efficient and systematic testing of compounds against ion channels during voltage-clamp. It has not, however, been adopted significantly in other important areas of ion channel research, where conventional patch-clamp remains the favored method. Here, we show the wider potential of the multiwell approach with the ability for efficient intracellular solution exchange, describing protocols and success rates for recording from a range of native and primary mammalian cells derived from blood vessels, arthritic joints and the immune and central nervous systems. The protocol involves preparing a suspension of single cells to be dispensed robotically into 4-8 microfluidic chambers each containing a glass chip with a small aperture. Under automated control, giga-seals and whole-cell access are achieved followed by preprogrammed routines of voltage paradigms and fast extracellular or intracellular solution exchange. Recording from 48 chambers usually takes 1-6 h depending on the experimental design and yields 16-33 cell recordings.

Towards a standardised metadata protocol for urban meteorological networks

With the growing number and significance of urban meteorological networks (UMNs) across the world, it is becoming critical to establish a standard metadata protocol. Indeed, a review of existing UMNs indicate large variations in the quality, quantity, and availability of metadata containing technical information (i.e., equipment, communication methods) and network practices (i.e., quality assurance/quality control and data management procedures). Without such metadata, the utility of UMNs is greatly compromised. There is a need to bring together the currently disparate sets of guidelines to ensure informed and well-documented future deployments. This should significantly improve the quality, and therefore the applicability, of the high-resolution data available from such networks. Here, the first metadata protocol for UMNs is proposed, drawing on current recommendations for urban climate stations and identified best practice in existing networks

Metacognitive control over memory processes under auditory distraction

Decades of research attest that memory processes suffer under conditions of auditory distraction. What is however less well understood is whether people are able to modify how their memory processes are deployed in order to compensate for disruptive effects of distraction. The metacognitive approach to memory describes a variety of ways people can exert control over their cognitive processes to optimize performance. Here we describe our recent investigations into how these control processes change under conditions of auditory distraction. We specifically looked at control of encoding in the form of decisions about how long to study a word when it is presented and control of memory reporting in the form of decisions whether to volunteer or withhold retrieved details. Regarding control of encoding, we expected that people would compensate for disruptive effects of distraction by extending study time under noise. Our results revealed, however, that when exposed to irrelevant speech, people curtail rather than extend study. Regarding control of memory reporting, we expected that people would compensate for the loss of access to memory records by volunteering responses held with lower confidence. Our results revealed, however, that people’s reporting strategies do not differ when memory task is performed in silence or under auditory distraction, although distraction seriously undermines people’s confidence in their own responses. Together, our studies reveal novel avenues for investigating the psychological effects of auditory distraction within a metacognitive framework.

Interplanetary magnetic field control of dayside auroral activity and the transfer of momentum across the dayside magnetopause

The orientation of the Interplanetary Magnetic Field (IMF) during transient bursts of ionospheric flow and auroral activity in the dayside auroral ionosphere is studied, using data from the EISCAT radar, meridian-scanning photometers, and an all-sky TV camera, in conjunction with simultaneous observations of the interplanetary medium by the IMP-8 satellite. It is found that the ionospheric flow and auroral burst events occur regularly (mean repetition period equal to 8.3 ± 0.6 min) during an initial period of about 45 min when the IMF is continuously and strongly southward in GSM coordinates, consistent with previous observations of the occurrence of transient dayside auroral activity. However, in the subsequent 1.5 h, the IMF was predominantly northward, and only made brief excursions to a southward orientation. During this period, the mean interval between events increased to 19.2 ± 1.7 min. If it is assumed that changes in the North-South component of the IMF are aligned with the IMF vector in the ecliptic plane, the delays can be estimated between such a change impinging upon IMP-8 and the response in the cleft ionosphere within the radar field-of-view. It is found that, to within the accuracy of this computed lag, each transient ionospheric event during the period of predominantly northward IMF can be associated with a brief, isolated southward excursion of the IMF, as observed by IMP-8. From this limited period of data, we therefore suggest that transient momentum exchange between the magnetosheath and the ionosphere occurs quasi-periodically when the IMF is continuously southward, with a mean period which is strikingly similar to that for Flux Transfer Events (FTEs) at the magnetopause. During periods of otherwise northward IMF, individual momentum transfer events can be triggered by brief swings to southward IMF. Hence under the latter conditions the periodicity of the events can reflect a periodicity in the IMF, but that period will always be larger than the minimum value which occurs when the IMF is strongly and continuously southward.

Improving mood with psychoanalytic and cognitive therapies (IMPACT): a pragmatic effectiveness superiority trial to investigate whether specialised psychological treatment reduces the risk for relapse in adolescents with moderate to severe unipolar depression: study protocol for a randomised controlled trial

Background Up to 70% of adolescents with moderate to severe unipolar major depression respond to psychological treatment plus Fluoxetine (20-50 mg) with symptom reduction and improved social function reported by 24 weeks after beginning treatment. Around 20% of non responders appear treatment resistant and 30% of responders relapse within 2 years. The specific efficacy of different psychological therapies and the moderators and mediators that influence risk for relapse are unclear. The cost-effectiveness and safety of psychological treatments remain poorly evaluated. Methods/Design Improving Mood with Psychoanalytic and Cognitive Therapies, the IMPACT Study, will determine whether Cognitive Behavioural Therapy or Short Term Psychoanalytic Therapy is superior in reducing relapse compared with Specialist Clinical Care. The study is a multicentre pragmatic effectiveness superiority randomised clinical trial: Cognitive Behavioural Therapy consists of 20 sessions over 30 weeks, Short Term Psychoanalytic Psychotherapy 30 sessions over 30 weeks and Specialist Clinical Care 12 sessions over 20 weeks. We will recruit 540 patients with 180 randomised to each arm. Patients will be reassessed at 6, 12, 36, 52 and 86 weeks. Methodological aspects of the study are systematic recruitment, explicit inclusion criteria, reliability checks of assessments with control for rater shift, research assessors independent of treatment team and blind to randomization, analysis by intention to treat, data management using remote data entry, measures of quality assurance, advanced statistical analysis, manualised treatment protocols, checks of adherence and competence of therapists and assessment of cost-effectiveness. We will also determine whether time to recovery and/or relapse are moderated by variations in brain structure and function and selected genetic and hormone biomarkers taken at entry. Discussion The objective of this clinical trial is to determine whether there are specific effects of specialist psychotherapy that reduce relapse in unipolar major depression in adolescents and thereby costs of treatment to society. We also anticipate being able to utilise psychotherapy experience, neuroimaging, genetic and hormone measures to reveal what techniques and their protocols may work best for which patients.

Varieties of semantic ‘access’ deficit in Wernicke’s aphasia and semantic aphasia

Comprehension deficits are common in stroke aphasia, including in cases with (i) semantic aphasia (SA), characterised by poor executive control of semantic processing across verbal and nonverbal modalities, and (ii) Wernicke’s aphasia (WA), associated with poor auditory-verbal comprehension and repetition, plus fluent speech with jargon. However, the varieties of these comprehension problems, and their underlying causes, are not well-understood. Both patient groups exhibit some type of semantic ‘access’ deficit, as opposed to the ‘storage’ deficits observed in semantic dementia. Nevertheless, existing descriptions suggest these patients might have different varieties of ‘access’ impairment – related to difficulty resolving competition (in SA) vs. initial activation of concepts from sensory inputs (in WA). We used a case-series design to compare WA and SA patients on Warrington’s paradigmatic assessment of semantic ‘access’ deficits. In these verbal and non-verbal matching tasks, a small set of semantically-related items are repeatedly presented over several cycles so that the target on one trial becomes a distractor on another (building up interference and eliciting semantic ‘blocking’ effects). WA and SA patients were distinguished according to lesion location in the temporal cortex, but in each group, some individuals had additional prefrontal damage. Both of these aspects of lesion variability – one that mapped onto classical ‘syndromes’ and one that did not – predicted aspects of the semantic ‘access’ deficit. Both SA and WA cases showed multimodal semantic impairment, although as expected the WA group showed greater deficits on auditory-verbal than picture judgements. Distribution of damage in the temporal lobe was crucial for predicting the initially beneficial effects of stimulus repetition: WA cases showed initial improvement with repetition of words and pictures, while in SA, semantic access was initially good but declined in the face of competition from previous targets. Prefrontal damage predicted the harmful effects of repetition: the ability to re-select both word and picture targets in the face of mounting competition was linked to left prefrontal damage in both groups. Therefore, SA and WA patients have partially distinct impairment of semantic ‘access’ but, across these syndromes, prefrontal lesions produce declining comprehension with repetition in both verbal and non-verbal tasks.

Ectomycorrhizal symbiosis can enhance plant nutrition through improved access to discrete organic nutrient patches of high resource quality

It is known that roots can respond to patches of fertility; however, root proliferation is often too slow to exploit resources fully, and organic nutrient patches may be broken down and leached, immobilized or chemically fixed before they are invaded by the root system. The ability of fungal hyphae to exploit resource patches is far greater than that of roots due to their innate physiological and morphological plasticity, which allows comprehensive exploration and rapid colonization of resource patches in soils. The fungal symbionts of ectomycorrhizal plants excrete significant quantities of enzymes such as chitinases, phosphatases and proteases. These might allow the organic residue to be tapped directly for nutrients such as N and P. Pot experiments conducted with nutrient-stressed ectomycorrhizal and control willow plants showed that when high quality organic nutrient patches were added, they were colonized rapidly by the ectomycorrhizal mycelium. These established willows (0.5 m tall) were colonized by Hebeloma syrjense P. Karst. for 1 year prior to nutrient patch addition. Within days after patch addition, colour changes in the leaves of the mycorrhizal plants (reflecting improved nutrition) were apparent, and after I month the concentration of N and P in the foliage of mycorrhizal plants was significantly greater than that in non-mycorrhizal plants subject to the same nutrient addition. It seems likely that the mycorrhizal plants were able to compete effectively with the wider soil microbiota and tap directly into the high quality organic resource patch via their extra-radical mycelium. We hypothesize that ectomycorrhizal plants may reclaim some of the N and P invested in seed production by direct recycling from failed seeds in the soil. The rapid exploitation of similar discrete, transient, high-quality nutrient patches may have led to underestimations when determining the nutritional benefits of ectomycorrhizal colonization.

Knowledge and perception of Ghanaian cocoa farmers on mirid control and their willingness to use forecasting systems

Annual losses of cocoa in Ghana to mirids are significant. Therefore, accurate timing of insecticide application is critical to enhance yields. However, cocoa farmers often lack information on the expected mirid population for each season to enable them to optimise pesticide use. This study assessed farmers’ knowledge and perceptions of mirid control and their willingness to use forecasting systems informing them of expected mirid peaks and time of application of pesticides. A total of 280 farmers were interviewed in the Eastern and Ashanti regions of Ghana with a structured open and closed ended questionnaire. Most farmers (87%) considered mirids as the most important insect pest on cocoa with 47% of them attributing 30-40% annual crop loss to mirid damage. There was wide variation in the timing of insecticide application as a result of farmers using different sources of information to guide the start of application. The majority of farmers (56%) do not have access to information on the type, frequency and timing of insecticides to use. However, respondents who are members of farmer groups had better access to such information. Extension officers were the preferred channel for information transfer to farmers with 72% of farmers preferring them to other available methods of communication. Almost all the respondents (99%) saw the need for a comprehensive forecasting system to help farmers manage cocoa mirids. The importance of accurate timing for mirid control based on forecasted information to farmer groups and extension officers was discussed.