Glutathione and the redox control system trypanothione/trypanothione reductase are involved in the protection of Leishmania spp. against nitrosothiol-induced cytotoxicity

Glutathione is the major intracellular antioxidant thiol protecting mammalian cells against oxidative stress induced by oxygen- and nitrogen-derived reactive species. In trypanosomes and leishmanias, trypanothione plays a central role in parasite protection against mammalian host defence systems by recycling trypanothione disulphide by the enzyme trypanothione reductase. Although Kinetoplastida parasites lack glutathione reductase, they maintain significant levels of glutathione. The aim of this study was to use Leishmania donovani trypanothione reductase gene mutant clones and different Leishmania species to examine the role of these two individual thiol systems in the protection mechanism against S-nitroso-N-acetyl-D,L-penicillamine (SNAP), a nitrogen-derived reactive species donor. We found that the resistance to SNAP of different species of Leishmania was inversely correlated with their glutathione concentration but not with their total low-molecular weight thiol content (about 0.18 nmol/10(7) parasites, regardless Leishmania species). The glutathione concentration in L. amazonensis, L. donovani, L. major, and L. braziliensis were 0.12, 0.10, 0.08, and 0.04 nmol/10(7) parasites, respectively. L. amazonensis, that have a higher level of glutathione, were less susceptible to SNAP (30 and 100 µM). The IC50 values of SNAP determined to L. amazonensis, L. donovani, L. major, and L. braziliensis were 207.8, 188.5, 160.9, and 83 µM, respectively. We also observed that L. donovani mutants carrying only one trypanothione reductase allele had a decreased capacity to survive (~40%) in the presence of SNAP (30-150 µM). In conclusion, the present data suggest that both antioxidant systems, glutathione and trypanothione/trypanothione reductase, participate in protection of Leishmania against the toxic effect of nitrogen-derived reactive species.

Learning about brain physiology and complexity from the study of the epilepsies

The brain is a complex system, which produces emergent properties such as those associated with activity-dependent plasticity in processes of learning and memory. Therefore, understanding the integrated structures and functions of the brain is well beyond the scope of either superficial or extremely reductionistic approaches. Although a combination of zoom-in and zoom-out strategies is desirable when the brain is studied, constructing the appropriate interfaces to connect all levels of analysis is one of the most difficult challenges of contemporary neuroscience. Is it possible to build appropriate models of brain function and dysfunctions with computational tools? Among the best-known brain dysfunctions, epilepsies are neurological syndromes that reach a variety of networks, from widespread anatomical brain circuits to local molecular environments. One logical question would be: are those complex brain networks always producing maladaptive emergent properties compatible with epileptogenic substrates? The present review will deal with this question and will try to answer it by illustrating several points from the literature and from our laboratory data, with examples at the behavioral, electrophysiological, cellular and molecular levels. We conclude that, because the brain is a complex system compatible with the production of emergent properties, including plasticity, its functions should be approached using an integrated view. Concepts such as brain networks, graphics theory, neuroinformatics, and e-neuroscience are discussed as new transdisciplinary approaches dealing with the continuous growth of information about brain physiology and its dysfunctions. The epilepsies are discussed as neurobiological models of complex systems displaying maladaptive plasticity.

Study of the comprehension of the scientific method by members of a university health research laboratory

In Brazil, scientific research is carried out mainly at universities, where professors coordinate research projects with the active participation of undergraduate and graduate students. However, there is no formal program for the teaching/learning of the scientific method. The objective of the present study was to evaluate the comprehension of the scientific method by students of health sciences who participate in scientific projects in an academic research laboratory. An observational descriptive cross-sectional study was conducted using Edgar Morin complexity as theoretical reference. In a semi-structured interview, students were asked to solve an abstract logical puzzle - TanGram. The collected data were analyzed using the hermeneutic-dialectic analysis method proposed by Minayo and discussed in terms of the theoretical reference of complexity. The students’ concept of the scientific method is limited to participation in projects, stressing the execution of practical procedures as opposed to scientific thinking. The solving of the TanGram puzzle revealed that the students had difficulties in understanding questions and activities focused on subjects and their processes. Objective answers, even when dealing with personal issues, were also reflected on the students’ opinions about the characteristics of a successful researcher. Students’ difficulties concerning these issues may affect their scientific performance and result in poorly designed experiments. This is a preliminary study that should be extended to other centers of scientific research.

Impact of specimen adequacy on the assessment of renal allograft biopsy specimens

The Banff classification was introduced to achieve uniformity in the assessment of renal allograft biopsies. The primary aim of this study was to evaluate the impact of specimen adequacy on the Banff classification. All renal allograft biopsies obtained between July 2010 and June 2012 for suspicion of acute rejection were included. Pre-biopsy clinical data on suspected diagnosis and time from renal transplantation were provided to a nephropathologist who was blinded to the original pathological report. Second pathological readings were compared with the original to assess agreement stratified by specimen adequacy. Cohen's kappa test and Fisher's exact test were used for statistical analyses. Forty-nine specimens were reviewed. Among these specimens, 81.6% were classified as adequate, 6.12% as minimal, and 12.24% as unsatisfactory. The agreement analysis among the first and second readings revealed a kappa value of 0.97. Full agreement between readings was found in 75% of the adequate specimens, 66.7 and 50% for minimal and unsatisfactory specimens, respectively. There was no agreement between readings in 5% of the adequate specimens and 16.7% of the unsatisfactory specimens. For the entire sample full agreement was found in 71.4%, partial agreement in 20.4% and no agreement in 8.2% of the specimens. Statistical analysis using Fisher's exact test yielded a P value above 0.25 showing that - probably due to small sample size - the results were not statistically significant. Specimen adequacy may be a determinant of a diagnostic agreement in renal allograft specimen assessment. While additional studies including larger case numbers are required to further delineate the impact of specimen adequacy on the reliability of histopathological assessments, specimen quality must be considered during clinical decision making while dealing with biopsy reports based on minimal or unsatisfactory specimens.

Role of food safety in procedures adopted for the purchase of minimally processed and fresh vegetables by foodservices

This research was designed to analyze whether the procedures adopted by foodservice establishments for the purchase of minimally processed and fresh vegetables favor the acquisition of safe products. This research investigated the purchasing policies of such establishments, whether self-managed or administered by foodservice contractors, in the municipality of Campinas and its outlying districts. A random sample of thirty-nine establishments participated in the research. The instruments for data collection were pre-tested, and the actual interviews were conducted by trained personnel. Comparative analyses were made using various statistical tests. All of the participating establishments purchase fresh vegetables, although only six of them use minimally processed ones. For most of the establishments, price is at least one of the most important criteria for the selection of a supplier, and they do not normally monitor the safety of the fresh products purchased (51.3%), nor do they make regular technical visits to guarantee quality (46.2%); moreover, most do not carry out a supplier development program. It is suggested that routine technical visits to suppliers should be adopted, as well as the creation of courses, such as those dealing with the safety of vegetables and supplier development, to be offered to foodservices.

Language-specific aspects of reading acquisition: the case of Russian

We have investigated Russian children’s reading acquisition during an intermediate period in their development: after literacy onset, but before they have acquired well-developed decoding skills. The results of our study suggest that Russian first graders rely primarily on phonemes and syllables as reading grain-size units. Phonemic awareness seems to have reached the metalinguistic level more rapidly than syllabic awareness after the onset of reading instruction, the reversal which is typical for the initial stages of formal reading instruction creating external demand for phonemic awareness. Another reason might be the inherent instability of syllabic boundaries in Russian. We have shown that body-coda is a more natural representation of subsyllabic structure in Russian than onset-rime. We also found that Russian children displayed variability of syllable onset and offset decisions which can be attributed to the lack of congruence between syllabic and morphemic word division in Russian. We suggest that fuzziness of syllable boundary decisions is a sign of the transitional nature of this stage in the reading development and it indicates progress towards an awareness of morphologically determined closed syllables. Our study also showed that orthographic complexity exerts an influence on reading in Russian from the very start of reading acquisition. Besides, we found that Russian first graders experience fluency difficulties in reading orthographically simple words and nonwords of two and more syllables. The transition from monosyllabic to bisyllabic lexical items constitutes a certain threshold, for which the syllabic structure seemed to be of no difference. When we compared the outcomes of the Russian children with the ones produced by speakers of other languages, we discovered that in the tasks which could be performed with the help of alphabetic recoding Russian children’s accuracy was comparable to that of children learning to read in relatively shallow orthographies. In tasks where this approach works only partially, Russian children demonstrated accuracy results similar to those in deeper orthographies. This pattern of moderate results in accuracy and excellent performance in terms of reaction times is an indication that children apply phonological recoding as their dominant strategy to various reading tasks and are only beginning to develop suitable multiple strategies in dealing with orthographically complex material. The development of these strategies is not completed during Grade 1 and the shift towards diversification of strategies apparently continues in Grade 2.

The impact of arms technology on military doctrines

Finnish Defence Studies is published under the auspices of the War College, and the contributions reflect the fields of research and teaching of the College. Finnish Defence Studies will occasionally feature documentation on Finnish Security Policy. Views expressed are those of the authors and do not necessarily imply endorsement by the War College.

Datenherrschaft – an Ethically Justified Solution to the Problem of Ownership of Patient Information

Patient information systems are crucial components for the modern healthcare and medicine. It is obvious that without them the healthcare cannot function properly – one can try to imagine how brain surgery could be done without using information systems to gather and show information needed for an operation. Thus, it can be stated that digital information is irremovable part of modern healthcare. However, the legal ownership of patient information lacks a coherent and justified basis. The whole issue itself is actually bypassed by controlling pa- tient information with different laws and regulations how patient information can be used and by whom. Nonetheless, the issue itself – who owns the patient in- formation – is commonly missed or bypassed. This dissertation show the problems if the legislation of patient information ownership is not clear. Without clear legislation, the outcome can be unexpected like it seems to be in Finland, Sweden and United Kingdom: the lack of clear regulation has come up with unwanted consequences because of problematic Eu- ropean Union database directive implementation in those countries. The legal ownership is actually granted to the creators of databases which contains the pa- tient information, and this is not a desirable situation. In healthcare and medicine, we are dealing with issues such as life, health and information which are very sensitive and in many cases very personal. Thus, this dissertation leans on four philosophical theories form Locke, Kant, Heidegger and Rawls to have an ethically justified basis for regulating the patient infor- mation in a proper way. Because of the problems of property and ownership in the context of information, a new concept is needed and presented to replace the concept of owning, that concept being Datenherrschaft (eng. mastery over in- formation). Datenherrschaft seems to be suitable for regulating patient infor- mation because its core is the protection of one’s right over information and this aligns with the work of the philosophers whose theories are used in the work. The philosophical argumentation of this study shows that Datenherrschaft granted to the patients is ethically acceptable. It supports the view that patient should be controlling the patient information about themselves unless there are such specific circumstance that justifies the authorities to use patient information to protect other people’s basic rights. Thus, if the patients would be legally grant- ed Datenherrschaft over patient information we would endorse patients as indi- viduals who have their own and personal experience of their own life and have a strong stance against any unjustified paternalism in healthcare. Keywords: patient information, ownership, Datenherrschaft, ethics, Locke, Kant, Heidegger, Rawls

Investigation into the determination of arsenic by direct current plasma atomic emission spectrometer

Improvements have been made on the currently available hydride generator system manufactured by SpectraMetrics Incorporated, because the system was found to be unsatisfactory with respect to the following: 1. the drying agent, anhydrous calcium chloride, 2. the special sample tube, 3. the direction of argon flow through the Buchner funnel when it came to dealing with real sample, that is, with reference only to aqueous extracts of soil samples. Changes that were made on the system included the replacement of anhydrous calcium chloride with anhydrous calcium sulphate and the replacement of the special sample tube with a modified one made from silica. Re-directing the flow of argon through the top of the Buchner funnel appeared to make the system compatible with aqueous extracts of soil samples. The interferences from 1000 ~g/mL of nickel(II) , cobalt(II), iron(III), copper(II) have been eliminated with the aid of 1.4 M hydrochloric acid and 1% (weight/volume) L-cystine. Greater than 90% recovery of 0.3 ~g/mL arsenic signal was achieved in each case. Furthermore, 103% of arsenic signal was accomplished in the presence of 1000 ~g/mL cadmium with 5 M Hel. tVhen each of the interferents was present in solution at 1000 ppm, a recovery of 85% was achieved by using 5 M hydrochloric acid and 3% (weight/volume) L-cystine. Without L-cystine and when 1.4 M hydrochloric acid was used, the recoveries were 0% (Ni), 0% (Co), 88% (Fe), 15% (Cu), 18% (Cd). Similarly, a solution containing 1000 ppm of each interferent gave a zero percent recovery of arsenic. The reduction of trivalent and pentavalent arsenic at a pH less than one has also been investigated and shown to be quantitative if peak areas are measured. The reproducibility determination of a 0.3 Vg/mL standard arsenic solution by hydride generation shows a relative standard deviation of 3.4%. The detection limits with and without Porapak Q have been found to be 0.6 ng/mL and 1.0 ng/mL, respectively.

The nature of avidyÄ in Buddhism and VedÄ nta

This thesis deals with the nature of ignorance as it was interpreted in the Upani~adic tradition, specifically in Advaita Vedanta, and in early and Mahayana Buddhism , e specially in the Madhyamika school of Buddhism. The approach i s a historical and comparative one. It examines the early thoughts of both the upanis.a ds and Buddhism abou t avidya (ignorance), shows how the notion was treated by the more speculative and philosphically oriented schools which base d themselves on the e arly works, and sees how their views differ. The thesis will show that the Vedinta tended to treat avidya as a topic for metaphysical s peculation as t he s chool developed, drifting from its initial e xistential concerns, while the Madhyamika remained in contact with the e xistential concerns evident in the first discourses of the Buddha. The word "notion" has been chosen for use in referring t o avidya, even though it may have non-intellectual and emotional connotations, to avoid more popular a lternatives such as "concept" or "idea". In neither the Upani,ads, Advaita Vedanta, or Buddhism is ignorance merely a concept or an idea. Only in a secondary sense, in texts and speech , does it become one. Avidya has more to do with the lived situation in which man finds himself, with the subjectobject separation in which he f eels he exists, than with i i i intel lect ual constr ucts . Western thought has begun to r ealize the same with concerns such as being in modern ontology, and has chosen to speak about i t i n terms of the question of being . Avidya, however, i s not a 'question' . If q ue stions we r e to be put regarding the nature of a vidya , they would be more of t he sort "What is not avidya?", though e ven here l anguage bestows a status t o i t which avidya does not have. In considering a work of the Eastern tradition, we f ace t he danger of imposing Western concepts on it. Granted t hat avidya is customari ly r endered i n English as ignorance, the ways i n which the East and West view i gno rance di f f er. Pedagogically , the European cultures, grounded in the ancient Greek culture, view ignorance as a l ack or an emptiness. A child is i gnorant o f certain t hings and the purpose o f f ormal education , in f act if not in theory, is to fill him with enough knowledge so that he can cope wit h t he complexities and the e xpectations of s ociety. On another level, we feel t hat study and research will l ead t o the discovery o f solutions, which we now lack , for problems now defying solut i on . The East, on the o t her hand, sees avidya in a d i fferent light.Ignorance isn't a lack, but a presence. Religious and philosophical l iterature directs its efforts not towards acquiring something new, but at removing t.he ideas and opinions that individuals have formed about themselves and the world. When that is fully accomplished, say the sages , t hen Wisdom, which has been obscured by those opinions, will present itself. Nothing new has to be learned, t hough we do have t o 'learn' that much. The growing interest in t he West with Eastern religions and philosophies may, in time, influence our theoretical and practical approaches to education and learning, not only in the established educati onal institutions, but in religious , p sychological, and spiritual activities as well. However, the requirements o f this thesis do no t permit a formulation of revolutionary method or a call to action. It focuses instead on the textual arguments which attempt to convince readers that t he world in which they take themselves to exist is not, in essence, real, on the ways i n which the l imitations of language are disclosed, and on the provisional and limited schemes that are built up to help students see through their ignorance. The metaphysic s are provisional because they act only as spurs and guides. Both the Upanisadic and Buddhist traditions that will be dealt with here stress that language constantly fails to encompass the Real. So even terms s uch as 'the Real', 'Absolute', etc., serve only to lead to a transcendent experience . The sections dealing with the Upanisads and Advaita Vedanta show some of the historical evolution of the notion of avidya, how it was dealt with as maya , and the q uestions that arose as t o its locus. With Gau?apada we see the beginnings of a more abstract treatment of the topic, and , the influence of Buddhism. Though Sankhara' S interest was primarily directed towards constructing a philosophy to help others attain mok~a ( l iberation), he too introduced t echnica l t e rminology not found in the works of his predecessors. His work is impressive , but areas of it are incomplete. Numbers of his followers tried to complete the systematic presentation of his insi ghts . Their work focuses on expl anat i ons of adhyasa (superimposition ) , t he locus and object of ignorance , and the means by which Brahman takes itself to be the jiva and the world. The section on early Buddhism examines avidya in the context o f the four truths, together with dubkha (suffering), the r ole it p l ays in t he chain of dependent c ausation , a nd t he p r oblems that arise with t he doctrine of anatman. With t he doct rines of e arly Buddhism as a base, the Madhyamika elaborated questions that the Buddha had said t e nded not t o edi f ication. One of these had to do with own - being or svabhava. Thi s serves a s a centr e around which a discussion o f i gnorance unfolds, both i ndividual and coll ective ignorance. There follows a treatment of the cessation of ignorance as it is discussed within this school . The final secti on tries to present t he similarities and differences i n the natures o f ignorance i n t he two traditions and discusses the factors responsible for t hem . ACKNOWLEDGEMENTS I would like to thank Dr. Sinha for the time spent II and suggestions made on the section dealing with Sankara and the Advait.a Vedanta oommentators, and Dr. Sprung, who supervised, direoted, corrected and encouraged the thesis as a whole, but especially the section on Madhyamika, and the final comparison.

"Welcome to my life" : the experiences of single mothers who are the recipients of multiple state provided benefits

Abstract This research takes the lens of social reproduction as a starting point for an examination of the effects of recent social welfare reforms on the lives o.fsingle mothers. As the cumulative effects o.f diminishing state provided benefits take hold, tensions are heightened as single mothers internalize the insecurity of earning an income in 11 capitalist labour market, while trying to carry out all that is involved in social reproduction with inadequate means of survival. Through interviewing single mothers who are the recipients of mUltiple state provided benefits (social assistance, student loans, subsidized housing and subsidized childcare), this thesis illuminates the cOl1linued regulation of women in an effort to assure that social reproduction is occurring at the lowest cost possible. State provided benefits are set lip in such a way that it is near impossible for single mothers to make ends meet without entering the labour force or entering into co-residential relationships. This push towards the labour force and/or marriage via punitive welfare policies illuminates the devaluation of the labour that is done at home. Through interviewing 5 single mothers, I will demonstrate the extensive labour that goes into maintaining their households. In addition .J case managers are interviewed. The employees of social assistance, subsidized hOllsing, subsidized childcare and student loans, have much agency in deeming who is worthy of receiving benefits. The employees of these agencies have the ability to make these women's lives easier or more complicated by how the workers interpret the policy regulations. Social policies are of paramount importance in the quest for women's equality and thus have consequences for how women's daily lives are organized. The rules and regulations that govern the individual policies are complex and bureaucratic and have implications for the ways in which women must organize their lives in order to survive. The shifts in social policy have been guided by neo-liberal assumptions with a focus on individual responsibility and a market-modeled welfare state. The caring work that is involved in raising children to be productive in a capitalist society is ignored or devalued in current policies. The emphasis in each polic.:v is on getting women who receive benefits into the paid work force, with little facilitation or investment into the caring work these women do on a daily basis that in turn supports capitalism. Policies, such as social assistance, subsidized housing, subsidized childcare and student loans, are set up in such a way that ignores the reality of women's day-to-day lives and devalues the necessary work done at home. It takes an abundance of labour and strategizing for women to seek out necessary means of survival, labour that is amplified when a woman is dealing with mUltiple slate provided benefits.