A Geographical Study of Language Borders in Wales and Brittany

Making particular use of cartographic methods, the study analyses the process of language-shift in two localities, one near Oswestry in the Welsh Borderland and the other near Chatelaudren in Cotes-du-Nord, Brittany. Both areas are situated on the line of linguistic divides, as traditionally recognised. The assumption is made that the geographer's methods may realistically be applied in the analysis of the abstract characteristics of language, so long as a distance-scale and a time-scale commensurate with the scale of the process are selected. This necessitates the discarding of census data on Welsh speaking, and no official statistics on the speaking of Breton are available. Instead, a 100% sample of "households with one or more members able to speak Welsh or Breton" is obtained, providing detailed information on the potential for the speaking of these languages in different parts of the study areas. The distribution of speakers is related to the influence of a series of variables, including topography, accessibility, settlement and communications patterns, employment and demographic characteristics. Against the potential are set two measures of the actual use of the two languages. Two pieces of information on actual use are obtained by questionnaire sample: first, the frequency of Welsh or Breton use by individuals; secondly, the variety of speaking situations (for example, home, workplace) where these languages are spoken. Cartographic comparison reveals areas showing anomalies between potential and actual use, and raises the question whether critical threshold numbers and proportions of speakers are necessary to promote or prevent language shifts. Particular attention is given to aspects of migration as an influence on thresholds and patterns of language use. A further stage of the survey examines opinion on the state of survival of Welsh and Breton in the two areas and the influence which opinion may have on the continued use of either language as the shift progresses. The two areas produce many contrasting results. Differences in attitudes to language use in the two areas are attributed partly to historical influences and partly to the differing status of the two languages, both within the study areas and in the national context. The Breton area appears to be at a more advanced stage of shift than the Welsh one. In both cases, knowledge of the state of decay of the two languages is found to be only slight, and is inaccurate except in the most general terms. Extraneous factors such as communications or employment patterns seem to exert a greater influence on language change than do local opinions on language survival. The linguistic divide is seen to be a complex zone within which speaking groups maintain or forfeit their language according to the degree of group communication which they can maintain. It is concluded that even at the most local of scales, language areas exhibit spatial features such as cores and fringes of intensity of language use, and that geographical and cartographic methods may make a significant contribution to the analysis of linguistic processes if an appropriate scale is employed for the collection and analysis of information

The load shedding advisor: An example of a crisis-response expert system

A Prolog-based prototype expert system is described that was implemented by the Network Operations Branch of the NASA Goddard Space Flight Center. The purpose of the prototype was to test whether a small, inexpensive computer system could be used to host a load shedding advisor, a system which would monitor major physical environment parameters in a computer facility, then recommend appropriate operator reponses whenever a serious condition was detected. The resulting prototype performed significantly to efficiency gains achieved by replacing a purely rule-based design methodology with a hybrid approach that combined procedural, entity-relationship, and rule-based methods

Spatio-Temporal Patterns in kdr Frequency in Permethrin and DDT Resistant Anopheles gambiae s.s. from Uganda

The planned upscaling of vector control strategies requires insight into the epidemiological consequences of vector resistance. Therefore, the pyrethroid and DDT resistance status of Anopheles gambiae s.l. was assessed in Uganda from 2004 to 2006, and spatial and seasonal variations in knockdown resistance (kdr) frequencies were analyzed in terms of epidemiological significance. Anopheles gambiae s.l. was DDT and pyrethroid resistant in central and eastern Uganda. The L1014S kdr allele frequencies varied from 3% to 48% in An. gambiae s.s. Although the homozygous resistant genotype was the most prevalent genotype among survivors, the genotypes could not entirely explain the bioassay results. In the dry season, the kdr frequency was significantly higher in Plasmodium falciparum-infected mosquitoes, indicating that mosquitoes bearing a kdr mutation have a better adult survival, hence a higher likelihood of becoming infectious. This study showed that kdr might have an epidemiological impact that could jeopardize the vector control strategies

The Design and Validation of the Quantum Mechanics Conceptual Survey

The Quantum Mechanics Conceptual Survey (QMCS) is a 12-question survey of students' conceptual understanding of quantum mechanics. It is intended to be used to measure the relative effectiveness of different instructional methods in modern physics courses. In this paper we describe the design and validation of the survey, a process that included observations of students, a review of previous literature and textbooks and syllabi, faculty and student interviews, and statistical analysis. We also discuss issues in the development of specific questions, which may be useful both for instructors who wish to use the QMCS in their classes and for researchers who wish to conduct further research of student understanding of quantum mechanics. The QMCS has been most thoroughly tested in, and is most appropriate for assessment of (as a posttest only), sophomore-level modern physics courses. We also describe testing with students in junior quantum courses and graduate quantum courses, from which we conclude that the QMCS may be appropriate for assessing junior quantum courses, but is not appropriate for assessing graduate courses. One surprising result of our faculty interviews is a lack of faculty consensus on what topics should be taught in modern physics, which has made designing a test that is valued by a majority of physics faculty more difficult than expected.Comment: Submitted to Physical Review Special Topics: Physics Education Researc

Distributed Subnetworks of Depression Defined by Direct Intracranial Neurophysiology

Major depressive disorder is a common and disabling disorder with high rates of treatment resistance. Evidence suggests it is characterized by distributed network dysfunction that may be variable across patients, challenging the identification of quantitative biological substrates. We carried out this study to determine whether application of a novel computational approach to a large sample of high spatiotemporal resolution direct neural recordings in humans could unlock the functional organization and coordinated activity patterns of depression networks. This group level analysis of depression networks from heterogenous intracranial recordings was possible due to application of a correlational model-based method for inferring whole-brain neural activity. We then applied a network framework to discover brain dynamics across this model that could classify depression. We found a highly distributed pattern of neural activity and connectivity across cortical and subcortical structures that was present in the majority of depressed subjects. Furthermore, we found that this depression signature consisted of two subnetworks across individuals. The first was characterized by left temporal lobe hypoconnectivity and pathological beta activity. The second was characterized by a hypoactive, but hyperconnected left frontal cortex. These findings have applications toward personalization of therapy

AR2, a novel automatic muscle artifact reduction software method for ictal EEG interpretation: Validation and comparison of performance with commercially available software.

Objective: To develop a novel software method (AR2) for reducing muscle contamination of ictal scalp electroencephalogram (EEG), and validate this method on the basis of its performance in comparison to a commercially available software method (AR1) to accurately depict seizure-onset location. Methods: A blinded investigation used 23 EEG recordings of seizures from 8 patients. Each recording was uninterpretable with digital filtering because of muscle artifact and processed using AR1 and AR2 and reviewed by 26 EEG specialists. EEG readers assessed seizure-onset time, lateralization, and region, and specified confidence for each determination. The two methods were validated on the basis of the number of readers able to render assignments, confidence, the intra-class correlation (ICC), and agreement with other clinical findings. Results: Among the 23 seizures, two-thirds of the readers were able to delineate seizure-onset time in 10 of 23 using AR1, and 15 of 23 using AR2 (

Heat shock protein Grp78/BiP/HspA5 binds directly to TDP-43 and mitigates toxicity associated with disease pathology

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with no cure or effective treatment in which TAR DNA Binding Protein of 43 kDa (TDP-43) abnormally accumulates into misfolded protein aggregates in affected neurons. It is widely accepted that protein misfolding and aggregation promotes proteotoxic stress. The molecular chaperones are a primary line of defense against proteotoxic stress, and there has been long-standing interest in understanding the relationship between chaperones and aggregated protein in ALS. Of particular interest are the heat shock protein of 70 kDa (Hsp70) family of chaperones. However, defining which of the 13 human Hsp70 isoforms is critical for ALS has presented many challenges. To gain insight into the specific Hsp70 that modulates TDP-43, we investigated the relationship between TDP-43 and the Hsp70s using proximity-dependent biotin identification (BioID) and discovered several Hsp70 isoforms associated with TDP-43 in the nucleus, raising the possibility of an interaction with native TDP-43. We further found that HspA5 bound specifically to the RNA-binding domain of TDP-43 using recombinantly expressed proteins. Moreover, in a Drosophila strain that mimics ALS upon TDP-43 expression, the mRNA levels of the HspA5 homologue (Hsc70.3) were significantly increased. Similarly we observed upregulation of HspA5 in prefrontal cortex neurons from human ALS patients. Finally, overexpression of HspA5 in Drosophila rescued TDP-43-induced toxicity, suggesting that upregulation of HspA5 may have a compensatory role in ALS pathobiology

Crystal structure of the human, FIC-Domain containing protein HYPE and implications for its functions

Protein AMPylation, the transfer of AMP from ATP to protein targets, has been recognized as a new mechanism of host-cell disruption by some bacterial effectors that typically contain a FIC-domain. Eukaryotic genomes also encode one FIC-domain protein, HYPE, which has remained poorly characterized. Here we describe the structure of human HYPE, solved by X-ray crystallography, representing the first structure of a eukaryotic FIC-domain protein. We demonstrate that HYPE forms stable dimers with structurally and functionally integrated FIC-domains and with TPR-motifs exposed for protein-protein interactions. As HYPE also uniquely possesses a transmembrane helix, dimerization is likely to affect its positioning and function in the membrane vicinity. The low rate of autoAMPylation of the wild-type HYPE could be due to autoinhibition, consistent with the mechanism proposed for a number of putative FIC AMPylators. Our findings also provide a basis to further consider possible alternative cofactors of HYPE and distinct modes of target-recognition

Addressing the under-reporting of adverse drug reactions in public health programs controlling HIV/AIDS, tuberculosis and malaria: A prospective cohort study

Background Adverse Drug Reactions (ADRs) are a major clinical and public health problem world-wide. The prompt reporting of suspected ADRs to regulatory authorities to activate drug safety surveillance and regulation appears to be the most pragmatic measure for addressing the problem. This paper evaluated a pharmacovigilance (PV) training model that was designed to improve the reporting of ADRs in public health programs treating the Human Immunodeficiency Virus (HIV), Tuberculosis (TB) and Malaria. Methods A Structured Pharmacovigilance and Training Initiative (SPHAR-TI) model based on the World Health Organization accredited Structured Operational Research and Training Initiative (SOR-IT) model was designed and implemented over a period of 12 months. A prospective cohort design was deployed to evaluate the outcomes of the model. The primary outcomes were knowledge gained and Individual Case Safety Reports (ICSR) (completed adverse drug reactions monitoring forms) submitted, while the secondary outcomes were facility based Pharmacovigilance Committees activated and health facility healthcare workers trained by the participants. Results Fifty-five (98%) participants were trained and followed up for 12 months. More than three quarter of the participants have never received training on pharmacovigilance prior to the course. Yet, a significant gain in knowledge was observed after the participants completed a comprehensive training for six days. In only seven months, 3000 ICSRs (with 100% completeness) were submitted, 2,937 facility based healthcare workers trained and 46 Pharmacovigilance Committees activated by the participants. Overall, a 273% increase in ICSRs submission to the National Agency for Food and Drug Administration and Control (NAFDAC) was observed. Conclusion Participants gained knowledge, which tended to increase the reporting of ADRs. The SPHAR-TI model could be an option for strengthening the continuous reporting of ADRs in public health programs in resource limited settings