Depicting community perspectives: repeat photography and participatory research as tools for assessing environmental services in Sagarmatha National Park, Nepal

Efforts have been made to provide a scientific basis for using environmental services as a conceptual tool to enhance conservation and improve livelihoods in protected mountain areas (MtPAS). Little attention has been paid to participatory research or locals’ concerns as environmental service (ES) users and providers. Such perspectives can illuminate the complex interplay between mountain ecosystems, environmental services and the determinants of human well-being. Repeat photography, long used in geographical fieldwork, is new as a qualitative research tool. This study uses a novel application of repeat photography as a diachronic photo-diary to examine local perceptions of change in ES in Sagarmatha National Park. Results show a consensus among locals on adverse changes to ES, particularly protection against natural hazards, such as landslides and floods, in the UNESCO World Heritage Site. We argue that our methodology could complement biophysical ecosystem assessments in MtPAS, especially since assessing ES, and acting on that, requires integrating diverse stakeholders’ knowledge, recognizing power imbalances and grappling with complex social-ecological systems.

Multiple B-cell clones producing antibodies directed to the spacer and disintegrin/thrombospondin type-1 repeat 1 (TSP1) of ADAMTS13 in a patient with acquired thrombotic thrombocytopenic purpura

BACKGROUND: The cysteine-rich/spacer domains of ADAMTS13 contain a major binding site for antibodies in patients with acquired thrombotic thrombocytopenic purpura (TTP). OBJECTIVE: To study the heterogeneity of the antibody response towards these domains an immunoglobulin V-gene phage-display library was constructed to isolate monoclonal anti-ADAMTS13 antibodies from the immunoglobulin repertoire of a patient with acquired TTP. METHODS: Combined variable heavy chain (VH) and variable light chain (VL) segments, expressed as single-chain Fv fragments (scFv), were selected for binding to an ADAMTS13 fragment consisting of the disintegrin/thrombospondin type-1 repeat 1 (TSP1)/cysteine-rich/spacer domains. RESULTS: Seven different scFv antibody clones were identified that were assigned to four groups based on their homology to VH germline gene segments. Epitope-mapping revealed that scFv I-9 (VH1-69), I-26 (VH1-02), and I-41 (VH3-09) bind to an overlapping binding site in the ADAMTS13 spacer domain, whereas scFv I-16 (VH3-07) binds to the disintegrin/TSP1 domains. The affinity of scFv for the disintegrin/TSP1/cysteine-rich/spacer domain was determined by surface plasmon resonance analysis and the dissociation constants ranged from 3 to 254 nM. The scFv partially inhibited ADAMTS13 activity. However, full-length IgG prepared from the variable domains of scFv I-9 inhibited ADAMTS13 activity more profoundly. Plasma of six patients with acquired TTP competed for binding of scFv I-9 to ADAMTS13. CONCLUSION: Our data indicate that multiple B-cell clones producing antibodies directed against the spacer domain are present in the patient analyzed in this study. Our findings also suggest that antibodies with a similar epitope specificity as scFv I-9 are present in plasma of other patients with acquired TTP.

Decreased EEG synchronization in Alzheimer's disease and mild cognitive impairment

The hypothesis of a functional disconnection of neuro-cognitive networks in patients with mild cognitive impairment (MCI) and Alzheimer Dementia was investigated using baseline resting EEG data. EEG databases from New York (264 subjects) and Stockholm (155 subjects), including healthy controls and patients with varying degrees of cognitive decline or Alzheimer Dementia were analyzed using Global Field Synchronization (GFS), a novel measure of global EEG synchronization. GFS reflects the global amount of phase-locked activity at a given frequency by a single number; it is independent of the recording reference and of implicit source models. Patients showed decreased GFS values in Alpha, Beta, and Gamma frequency bands, and increased GFS values in the Delta band, confirming the hypothesized disconnection syndrome. The results are discussed within the framework of current knowledge about the functional significance of the affected frequency bands.

Designed ankyrin repeat proteins as anti-idiotypic-binding molecules

According to the network theory antibodies may act as antigens thus generating anti-idiotypic antibodies that can function as regulators of immune responses. Designed ankyrin repeat proteins (DARPins) are a new class of binding proteins and may serve as an alternative to antibodies. Selections from large DARPin libraries against the variable regions of a murine monoclonal anti-human IgE antibody, termed BSW17, yielded two highly specific anti-idiotypic DARPins both with high affinity. Their binding characteristics were comparable with these of a previously selected anti-idiotypic antibody. In vitro cell assays showed that the anti-idiotypic DARPins were able to inhibit the binding of BSW17 to cell-bound IgE and prevented BSW17 functional activity. These experiments demonstrate the possibility to isolate anti-idiotypic DARPins recognizing idiotypic determinants analogous to antibodies. In the future these DARPins may be further analyzed for their potential as putative vaccine candidates.

Theta burst transcranial magnetic stimulation is associated with increased EEG synchronization in the stimulated relative to unstimulated cerebral hemisphere

Theta burst transcranial magnetic stimulation (TBS) may induce behavioural changes that outlast the stimulation period. The neurophysiological basis of these behavioural changes are currently under investigation. Given the evidence that cortical information processing relies on transient synchronization and desynchronization of neuronal assemblies, we set out to test whether TBS is associated with changes of neuronal synchronization as assessed by surface EEG. In four healthy subjects one TBS train of 600 pulses (200 bursts, each burst consisting of 3 pulses at 30 Hz, repeated at intervals of 100 ms) was applied over the right frontal eye field and EEG synchronization was assessed in a time-resolved manner over 60 min by using a non-overlapping moving window. For each time step the linear cross-correlation matrix for six EEG channels of the right and for the six homotopic EEG channels of the left hemisphere were computed and their largest eigenvalues used to assess changes of synchronization. Synchronization was computed for broadband EEG and for the delta, theta, alpha, beta and gamma frequency bands. In all subjects EEG synchronization of the stimulated hemisphere was significantly and persistently increased relative to EEG synchronization of the unstimulated hemisphere. This effect occurred immediately after TBS for the theta, alpha, beta and gamma frequency bands and 10-20 min after TBS for broadband and delta frequency band EEG. Our results demonstrate that TBS is associated with increased neuronal synchronization of the cerebral hemisphere ipsilateral to the stimulation site relative to the unstimulated hemisphere. We speculate that enhanced synchronization interferes with cortical information processing and thus may be a neurophysiological correlate of the impaired behavioural performance detected previously.

EpCAM-targeted delivery of nanocomplexed siRNA to tumor cells with designed ankyrin repeat proteins

Specific delivery to tumors and efficient cellular uptake of nucleic acids remain major challenges for gene-targeted cancer therapies. Here we report the use of a designed ankyrin repeat protein (DARPin) specific for the epithelial cell adhesion molecule (EpCAM) as a carrier for small interfering RNA (siRNA) complementary to the bcl-2 mRNA. For charge complexation of the siRNA, the DARPin was fused to a truncated human protamine-1 sequence. To increase the cell binding affinity and the amount of siRNA delivered into cells, DARPin dimers were generated and used as fusion proteins with protamine. All proteins expressed well in Escherichia coli in soluble form, yet, to remove tightly bound bacterial nucleic acids, they were purified under denaturing conditions by immobilized metal ion affinity chromatography, followed by refolding. The fusion proteins were capable of complexing four to five siRNA molecules per protamine, and fully retained the binding specificity for EpCAM as shown on MCF-7 breast carcinoma cells. In contrast to unspecific LipofectAMINE transfection, down-regulation of antiapoptotic bcl-2 using fusion protein complexed siRNA was strictly dependent on EpCAM binding and internalization. Inhibition of bcl-2 expression facilitated tumor cell apoptosis as shown by increased sensitivity to the anticancer agent doxorubicin.

Cortical local and long-range synchronization interplay in human absence seizure initiation

Brain activity relies on transient, fluctuating interactions between segregated neuronal populations. Synchronization within a single and between distributed neuronal clusters reflects the dynamics of these cooperative patterns. Thus absence epilepsy can be used as a model for integrated, large-scale investigation of the emergence of pathological collective dynamics in the brain. Indeed, spike-wave discharges (SWD) of an absence seizure are thought to reflect abnormal cortical hypersynchronization. In this paper, we address two questions: how and where do SWD arise in the human brain? Therefore, we explored the spatio-temporal dynamics of interactions within and between widely distributed cortical sites using magneto-encephalographic recordings of spontaneous absence seizures. We then extracted, from their time-frequency analysis, local synchronization of cortical sources and long-range synchronization linking distant sites. Our analyses revealed a reproducible sequence of 1) long-range desynchronization, 2) increased local synchronization and 3) increased long-range synchronization. Although both local and long-range synchronization displayed different spatio-temporal profiles, their cortical projection within an initiation time window overlap and reveal a multifocal fronto-central network. These observations contradict the classical view of sudden generalized synchronous activities in absence epilepsy. Furthermore, they suggest that brain states transition may rely on multi-scale processes involving both local and distant interactions.

Gravity-based Local Clock Synchronization in Wireless Sensor Networks

Contention-based MAC protocols follow periodic listen/sleep cycles. These protocols face the problem of virtual clustering if different unsynchronized listen/sleep schedules occur in the network, which has been shown to happen in wireless sensor networks. To interconnect these virtual clusters, border nodes maintaining all respective listen/sleep schedules are required. However, this is a waste of energy, if locally a common schedule can be determined. We propose to achieve local synchronization with a mechanism that is similar to gravitation. Clusters represent the mass, whereas synchronization messages sent by each cluster represent the gravitation force of the according cluster. Due to the mutual attraction caused by the clusters, all clusters merge finally. The exchange of synchronization messages itself is not altered by LACAS. Accordingly, LACAS introduces no overhead. Only a not yet used property of synchronization mechanisms is exploited.

Dynamic Synchronization: A Synchronization Model through Behavioral Reflection

In conventional software applications, synchronization code is typically interspersed with functional code, thereby impacting understandability and maintainability of the code base. At the same time, the synchronization defined statically in the code is not capable of adapting to different runtime situations. We propose a new approach to concurrency control which strictly separates the functional code from the synchronization requirements to be used and which adapts objects to be synchronized dynamically to their environment. First-class synchronization specifications express safety requirements, and a dynamic synchronization system dynamically adapts objects to different runtime situations. We present an overview of a prototype of our approach together with several classical concurrency problems, and we discuss open issues for further research.

Repeat chlamydia screening among adolescents: cohort study in a school-based programme in New Orleans

OBJECTIVES To describe uptake of chlamydia screening, determine rates of repeated yearly screening and investigate determinants of repeated participation in an organised school-based screening programme. METHODS The authors analysed data from 1995 to 2005 from female and male students in up to 13 schools in New Orleans, Louisiana, USA. The authors calculated proportions of students tested among all enrolled students and among those with parental consent and the percentage of positive chlamydia tests in each school year. The authors used random effects logistic regression to examine the effect of past screening history on subsequent participation. RESULTS 35 041 students were registered for at least one school year. Overall coverage was >30% in all school years. Among all students registered for 4 years, 10.6% (95% CI 9.3% to 12.0%) of women and 12.7% (95% CI 11.2% to 14.2%) of men had a test every year. Among students with parental consent for 4 years, 49.3% (95% CI 44.6% to 54.1%) of women and 59.3% (95% CI 54.5% to 64.0%) of men had a test every year. Among students registered for 2 or more years, those with a previous positive chlamydia test were less likely to have a subsequent test (female adjusted OR 0.77, 95% CI 0.67 to 0.88 and male adjusted OR 0.84, 95% CI 0.69 to 1.02). Chlamydia positivity increased over time. CONCLUSIONS High levels of uptake can be achieved in school-based chlamydia screening programmes, but repeated yearly screening is difficult to sustain over time.