The presence of colloids in groundwater can significantly affect contaminant migration. Therefore, the evaluation of the conditions in which the presence of colloids can favour contaminant migration is one of the most critical tasks for the assessment of the security of radioactive waste repositories. Colloids will be important for radionuclide migration towards the geosphere if they exist in non negligible concentration and if they are stable and mobile. Those aspects are strictly related to the geochemical conditions of the medium, which are of primary importance. In this work, we centred our attention on the uranium migration in a granitic fractured environment. Colloids were shown to be stable over months in low mineralized and alkaline waters (pH=9.7 and ionic strength 1·10-3 M). The transport of uranium in a granite fracture was studied, using a natural groundwater from the Grimsel Test Site (Switzerland) located in a granitic massive, in absence and presence of bentonite colloids. Results showed that the uranium migration was significantly affected by the presence of colloid in the medium.

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One of the world's oldest continuing societies, the Ju/'hoansi, or Bushmen of the Kalahari Desert offer profound insights into what is fundamental to human existence. In the face of outside pressures that threaten the complete disruption of their communal way of life, the Ju/'hoansi find deep spiritual resources in their traditional healing dance. Their indigenous method of healing individuals is also a powerful affirmation of the community, and has recently become a means of settling land and property disputes, problems that never existed in the old days. The healing dance promises to be the crucial factor that allows the Ju/'hoansi to preserve their culture into the 21st century. These inspiring people set an example for us to look beyond the false promises of modern technology in search of the spiritual healing that is so desperately needed in our own culture and within ourselves.


STUDENT LEARNING ASSESSMENT IN THE SOCIAL SCIENCES: ESTABLISHING A NATIONAL BASELINE FOR CRIMINAL JUSTICE PROGRAMS By Jennifer N. Jenkins, Ph.D. A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy at Virginia Commonwealth University. Virginia Commonwealth University, 2006 Major Director: Laura J. Moriarty, Ph.D. Acting Associate Vice Provost for Academic Affairs Office of the Provost This dissertation focuses on student learning outcomes assessment in criminal justice programs in American colleges and universities. Particularly, this research sought to establish a baseline understanding about how criminal justice programs are measuring student achievement toward learning outcomes. The baseline does not include what students should be learning or how that learning should be assessed; it includes only what is actually happening in criminal justice programs in terms of how student learning is being assessed. The baseline data were then compared to the results from two studies that focused on student learning assessment in political science departments and public relations programs in institutions of higher education. X The population for this research included 834 twoand four-year accredited institutions of higher education that offer a degree in criminal justice/criminology. A total of 369 criminal justice programs were included in the randomly-generated sample, and 44 percent of these programs completed the online questionnaire. The online survey instrument used for this research consists of 30 questions that are aligned with the "ideal type" of learning assessment model where a set of learning objectives are developed, assessment instruments are created and implemented, data are regularly collected and analyzed, and changes are made to improve the curriculum/instruction. The major findings of this research indicate that a large majority of criminal justice programs are assessing student learning to some degree, but many are using instruments that are documented as ineffective measures of assessment (e.g., grades, surveys, and Major Field Test). Also, a substantial number of criminal justice programs are located in institutions that place a high priority on learning assessment, but a small percentage of the programs reported that adequate resources are available for assessment purposes. Regardless of these factors, many criminal justice programs seem to be following the ideal type of learning assessment model where the process is completed by making changes to the curriculum and instruction to improve student learning and development. When compared to political science and public relations, it appears that criminal justice as an entire discipline is up to par in terms of its overall involvement in student learning assessment. Appendix A Initial IRB A ~ ~ r o v a l 183


AIM
To evaluate the impact of obesity on the posto-perative outcome after hepatic resection in patients with hepatocellular carcinoma (HCC).

METHODS
Data from 328 consecutive patients with primary HCC and 60 patients with recurrent HCC were studied. We compared the surgical outcomes between the non-obese group (body mass index: BMI < 25 kg/m(2)) and the obese group (BMI > or = 25 kg/m(2)).

RESULTS
Following curative hepatectomy in patients with primary HCC, the incidence of postoperative complications and the long-term prognosis in the non-obese group (n = 240) were comparable to those in the obese group (n = 88). Among patients with recurrent HCC, the incidence of postoperative complications after repeat hepatectomy was not significantly different between the non-obese group (n = 44) and the obese group (n = 16). However, patients in the obese group showed a significantly poorer long-term prognosis than those in the non-obese group (P < 0.05, five-year survival rate; 51.9% and 92.0%, respectively).

CONCLUSION
Obesity alone may not have an adverse effect on the surgical outcomes of patients with primary HCC. However, greater caution seems to be required when planning a repeat hepatectomy for obese patients with recurrent HCC.


Pretrained models from self-supervision are prevalently used in fine-tuning downstream tasks faster or for better accuracy. However, gaining robustness from pretraining is left unexplored. We introduce adversarial training into self-supervision, to provide general-purpose robust pretrained models for the first time. We find these robust pretrained models can benefit the subsequent fine-tuning in two ways: i) boosting final model robustness; ii) saving the computation cost, if proceeding towards adversarial fine-tuning. We conduct extensive experiments to demonstrate that the proposed framework achieves large performance margins (eg, 3.83% on robust accuracy and 1.3% on standard accuracy, on the CIFAR-10 dataset), compared with the conventional end-to-end adversarial training baseline. Moreover, we find that different self-supervised pretrained models have diverse adversarial vulnerability. It inspires us to ensemble several pretraining tasks, which boosts robustness more. Our ensemble strategy contributes to a further improvement of 3.59% on robust accuracy, while maintaining a slightly higher standard accuracy on CIFAR-10. Our codes are available at https://github.com/TAMU-VITA/Adv-SS-Pretraining.


This essay follows the assumption that the first principle of classical metaphysics has its counterpart in political sovereignty as suprema potestas. Therefore, both can be equally described as arché. Their epitome is the God of so-called ontotheology, who thus proves to be what I call the Ur-Arché. In contrast to current post-metaphysical approaches, however, I suggest overcoming ontotheology through a different metaphysics, which emphasizes the self-transcending surplus character of being. I regard early Christian martyrdom as an eminent way in which the surplus of being is manifested. This has two interwoven aspects, one ontological and one political, both arising from the excessive idea of the Christ event, or the notion that there is life beyond life unto death. I will analyse the mechanism allowing early Christian martyrs to counteract Roman imperial sovereignty. Finally, I will relate this to contemporary life systems in which sovereignty has become anonymous biopower.


Noting that the field of agro-food studies has undergone numerous 'turns' over the years, this article first seeks to make sense of this evolving literature by examining aspects of the metaphysical foreground upon which this 'turning' takes place. Doing this highlights a coalescing of sorts within the field; a movement the author describes as being less toward a specific theoretical framework as it is around a general way of doing agro-food scholarship. This style of scholarship embraces relationality, process, and multiplicity while emphasising the generative capacities of what agro-food scholars do for enacting novel political, ontological, and normative practices. The reminder of the article co-experiments with what it means to be open to these productive capacities as researchers, in terms of making the un-thought thinkable and un-doable routine. In doing this the article offers an account of agro-food imaginaries that is hopeful precisely because it is unsettling.


Researches regarding contamination with plant pathogens and pests, in specific rotation of agroforestry holdings on sandy soils, revealed the biological material and the climatic conditions as vulnerable points to infection. Determinations on Cowpea aphid borne virus infection in 144 cowpea genotypes, showsed a negative correlation between production and plant resistance to this pathogen, at 3-4 true leaves and flowering stages (r = - 0.792 **, r = 0.744 **). In peanut the presence of f fusarium wilt, produced by Fusarium oxysporum f.sp. vasinfectum, that caused sporadic drying plant, was signaled with a frequency of 2.25 to 22%, depending on the genotype. In maize symptoms of infection caused by Fusarium moniliforme, Ustilago maydis and attack produced by Rhopalosiphum maidis and Ostrinia nubilalis were signaled, the degree and frequency of attack being in relation to genotype. The climatic conditions of the years 2012 and 2013 have influenced in different ways the cowpea plants infection with Pseudomonas syringae pv. vignae (Da = 18.85 to 20.64%) and Uromyces appendiculatus (Da = 12.6 to 34.7%).


International Journal of Contemporary Education (IJCE) would like to acknowledge the following reviewers for their assistance with peer review of manuscripts for this issue. Many authors, regardless of whether IJCE publishes their work, appreciate the helpful feedback provided by the reviewers. Their comments and suggestions were of great help to the authors in improving the quality of their papers. Each of the reviewers listed below returned at least one review for this issue.Reviewers for Volume 6, Number 1 Ahmad Suradi, State Islamic Institute of Bengkulu, IndonesiaÁlvaro Manzano Redondo, UCJC University, SpainAurora Q. Pestano, University of San Jose Recoletos, PhilippinesBožić-Lenard Dragana, University of Osijek Croatia, CroatiaBruna Gabriela Augusto Marçal Vieira, CEFET-MG, BrazilCarme Pinya, University of Balearic Islands, SpainDina Radeljas, Mohawk Valley Community College, USAEdward Bolden, Case Western Reserve University, USAFroilan Delute Mobo, Philippine Merchant Marine Academy, PhilippinesGiuseppe Maugeri, University of Urbino, ItalyGraziano Serragiotto, Ca' Foscari University of Venice, ItalyIvan Lenard, Elementary School Ladimirevci, CroatiaLi Li, Bath Spa University, UKMatthew Schatt, University of Florida, USA William OscarEditorial AssistantInternational Journal of Contemporary Education------------------------------------------------------------Redfame Publishing9450 SW Gemini Dr. #99416Beaverton, OR 97008, USATel: 1-503-828-0536 ext. 509Fax: 1-503-828-0537E-mail 1: firstname.lastname@example.com 2: email@example.com: http://ijce.redfame.com


This paper argues that the common law of interstate nuisance remains an essential tool despite the rise of the modern regulatory state. In the rare cases when existing regulatory authorities fail to address emerging environmental problems, federal common law can serve as a backstop. When federal regulatory authorities are capable of addressing transboundary problems, but fail to do so, common law actions based on the law of source states remain a viable means of redress for states suffering significant harm from such pollution. Reconnecting the law of interstate nuisance to its historical roots, the paper concludes that the common law has been more effective as a "prod" to the development and implementation of new pollution control technology and to stimulate regulatory action to require its use, rather than as a vehicle for the judiciary to impose its own comprehensive solutions for transboundary environmental problems. Part I reviews the history of the common law of interstate nuisance from the early twentieth century through the rise of the modern regulatory state. Part II focuses on three contemporary interstate nuisance disputes – North Carolina's effort to reduce transboundary pollution from power plants operated by the Tennessee Valley Authority, Connecticut's efforts to reduce greenhouse gas emissions from utilities operating Midwestern coal-fired power plants, and efforts by Michigan and other states to stop invasive species of Asian carp from reaching the Great Lakes. Part III then reevaluates the common law of interstate nuisance in light of these precedents, finding that it still can be an effective catalyst for executive or legislative action to redress transboundary environmental harm.


BACKGROUND
Poly(ADP)-ribose polymerase (PARP) inhibitors such as olaparib can induce cell death in cancer cells with homologous recombination (HR) DNA repair deficiencies, such as BRCA1/2 mutations.

AIM
To identify prognostic biomarkers of long-term outcomes in cancer patients.

METHODS
Immunohistochemistry was used to analyse expression of key HR pathway proteins (ATM, ATR, BRCA1, MDC1, MRE11) and PARP-1 in 100 serous ovarian cancer (SOC) and 100 triple-negative breast cancer (TNBC) tumour samples from Japanese patients. RECIST assessment was used.

RESULTS
Patient demographic data and BRCA1/2 mutation status were unavailable. Most proteins listed previously were detected in > 80% of tissue samples, with BRCA1 expression detected in 60-65%. A potential link between BRCA1 expression and overall survival (M stage adjusted) in SOC patients was observed, but was not statistically significant after multiple testing adjustment. Correlations between other biomarker expression and survival were not observed. In TNBC patients, MDC1 staining was associated with progressive disease, but this was not statistically significant; the analysis did not identify significant correlations between biomarker expression and disease control. Limited event numbers prevented assessment of the prognostic value of BRCA1 in TNBC.

CONCLUSION
BRCA1 expression may be a candidate for a prognostic biomarker in SOC. Further studies are warranted.


In this paper, the author examines the current structure of the tax system for hydrocarbon production in Trinidad and Tobago in light of global trends in hydrocarbon taxation. Some of the main features of the tax regime are compared and benchmarked against what the literature has defined as best practices. The author calculates marginal effective tax rates, given assumptions of oil and gas prices and changes in tax incentives, and finds that tax levels are relatively adequate from an international perspective. Some of the more recent tax incentives, although helpful in terms of cash flow relief for companies, do not make as big of a difference to tax revenues and investment plans as do, for example, changes in international conditions when considered over the long run. Moreover, given the preeminence of natural gas in the economy, the tax system could be better modified to consider the special structural features of the gas market, while still encouraging investment in other energy sectors.


This report investigates corruption risk of EU funds spending in Hungary within the framework of the Public Procurement Law. Its finding is that in spite of what is a tight regulatory framework EU funds are likely to fuel the abuse of public spending. Even though public procurement using EU funds faces considerably more stringent regulation, their use poses much greater corruption risks when compared with funds procured domestically and corruption risks are particularly pronounced for large projects. The report also argues that large-scale institutionalized corruption in Hungary may be widespread and driven primarily by political cycles. Such corruption, often labelled "legal corruption", typically involves neither bribery nor collusion between lower level bureaucrats and private individuals; rather, it operates through contractual relationships which benefit the highest echelons of the political and business elite. There are a small number of new anti-corruption initiatives of the new government which entered office in 2010, but while they might indicate a positive step towards higher public sector integrity, their results are yet to be seen.


This paper surveys recent developments in the evaluation of point and density forecasts in the context of forecasts made by Vector Autoregressions. Specific emphasis is placed on highlighting those parts of the existing literature that are applicable to direct multi-step forecasts and those parts that are applicable to iterated multi-step forecasts. This literature includes advancements in the evaluation of forecasts in population (based on true, unknown model coefficients) and the evaluation of forecasts in the finite sample (based on estimated model coefficients). The paper then examines in Monte Carlo experiments the finite-sample properties of some tests of equal forecast accuracy, focusing on the comparison of VAR forecasts to AR forecasts. These experiments show the tests to behave as should be expected given the theory. For example, using critical values obtained by bootstrap methods, tests of equal accuracy in population have empirical size about equal to nominal size.


A broad distinction is proposed between cultural and sociological research into translation. Cultural research focuses on the level of ideas (or memes) while sociological research focuses on people and their observable behaviour. Some theoretical frameworks have been proposed for the analysis of some of the relevant sociological issues. However, their application has remained limited, and many areas are relatively neglected or undertheorized. These include research on team translation and teamwork revision processes, co-editing, institutional multilingual document production, translator-client relations, translation policy, translator networks, translators' use of technical and other resources, translator status and mobility, the discourse of translation, and accreditation systems. The central notion linking these areas is that of translation as a social practice.


Background: The present study assesses the frequency of injury in Europe's top-level judokas, during top-level competitions, and defines risk factors. Methods: The members of the EJU Medical Commission collected injury data over the period of 2005 to 2020 using the EJU Injury Registration Form at Europe's top judoka tournaments. Results: Over the 15 years of the study, 128 top-level competitions with 28,297 competitors were included; 699 injuries were registered. Of all competitors, 2.5% needed medical treatment. The knee (17.4%), shoulder (15.7%), and elbow (14.2%) were the most common anatomical locations of injury. Sprains (42.2%) were by far the most frequent injury type, followed by contusions (23.1%). Of all contestants, 0.48% suffered an injury which needed transportation to hospital. There was a statistically significant higher frequency of elbow injuries in female athletes (p < 0.01). Heavy-weight judokas suffered a remarkably low number of elbow injuries, with more knee and shoulder injuries. Light-weight judokas were more prone to elbow injuries. Conclusions: We found there was a low injury rate in top-level competitors, with a greater frequency of elbow injuries in female judokas. During the 15 years of injury collection data, an injury incidence of 2.5% was found, with a remarkable high injury rate in the women's −52 kg category, and statistically significantly more elbow injuries in women overall.


Introduction The accurate reproduction of clinical interventions and the evaluation of provider adherence in research publications improve the evaluation and implementation of research findings into clinical practice. We sought to examine the proportion of clinical pathway publications in an emergency department setting that adequately reported the following: (1) the exact reproduction of the clinical pathway that was implemented in the study, (2) the adherence to and correct execution of the clinical pathway intervention, and (3) the presence of a pre-implementation education phase. Methods We performed a descriptive systematic review of the literature from 2006 to 2015 using MEDLINE, EMBASE, CENTRAL, and CINAHL. All types of prospective trial designs were eligible. Validated clinical pathway criteria were used to identify relevant publications. Two reviewers independently collected data using a piloted data abstraction tool. Risk of bias was assessed using the Cochrane Effective Practice and Organization of Care Group Risk of Bias Tool and the Newcastle-Ottawa Scale. Results We identified 5947 publications, 44 of which met our inclusion criteria. The formal clinical pathway was fully reproduced in 27 (61%) publications, partially reproduced in 9 (21%), and not reproduced in 8 (18%). Only 14 (32%) studies reported whether at least one decision step was executed correctly. The presence of a pre-implementation education phase was reported in 33 (75%) studies. Conclusion The underreporting of intervention elements may present a barrier to both the evaluation and accurate replication of clinical pathway interventions. These finding may be useful for the elaboration of complex intervention reporting guidelines, improved reporting in future clinical pathway publications, and improved knowledge translation and exchange of clinical pathway interventions.


Around the globe, the COVID-19 pandemic has turned daily live upside down since social distancing is probably the most effective means of containing the virus until herd immunity is reached. Social norms have been shown to be an important determinant of social distancing behaviors. By conducting two experiments and using the priming method to manipulate social isolation recollections, we study whether social distancing has in turn affected norms of prosociality and norm compliance. The normative expectations of what behaviors others would approve or disapprove in our experimental setting did not change. Looking at actual behavior, however, we find that persistent social distancing indeed caused a decline in prosociality – even after the relaxation of social distancing rules and in times of optimism. At the same time, our results contain some good news since subjects seem still to care for norms and become more prosocial once again after we draw their attention to the empirical norm of how others have previously behaved in a similar situation.


OBJECTIVE The aim of this study was to present long-term seizure outcome data in a consecutive series of patients with refractory mesial temporal lobe epilepsy primarily treated with transsylvian selective amygdalohippocampectomy (SAHE). METHODS The authors retrospectively analyzed prospectively collected data for all patients who had undergone resective surgery for medically refractory epilepsy at their institution between July 1994 and December 2014. Seizure outcome was assessed according to the International League Against Epilepsy (ILAE) and the Engel classifications. RESULTS The authors performed an SAHE in 158 patients (78 males, 80 females; 73 right side, 85 left side) with a mean age of 37.1 ± 10.0 years at surgery. Four patients lost to follow-up and 1 patient who committed suicide were excluded from analysis. The mean follow-up period was 9.7 years. At the last available follow-up (or before reoperation), 68 patients (44.4%) had achieved an outcome classified as ILAE Class 1a, 46 patients (30.1%) Class 1, 6 patients (3.9%) Class 2, 16 patients (10.4%) Class 3, 15 patients (9.8%) Class 4, and 2 patients (1.3%) Class 5. These outcomes correspond to Engel Class I in 78.4% of the patients, Engel Class II in 10.5%, Engel Class III in 8.5%, and Engel Class IV in 2.0%. Eleven patients underwent a second surgery (anterior temporal lobectomy) after a mean of 4.4 years from the SAHE (left side in 6 patients, right side in 5). Eight (72.7%) of these 11 patients achieved seizure freedom. The overall ILEA seizure outcome since (re)operation after a mean follow-up of 10.0 years was Class 1a in 72 patients (47.0%), Class 1 in 50 patients (32.6%), Class 2 in 7 patients (4.6%), Class 3 in 15 patients (9.8%), Class 4 in 8 patients (5.2%), and Class 5 in 1 patient (0.6%). These outcomes correspond to an Engel Class I outcome in 84.3% of the patients. CONCLUSIONS A satisfactory long-term seizure outcome following transsylvian SAHE was demonstrated in a selected group of patients with refractory temporal lobe epilepsy.


The evolution of roughness as a function of surface age was used to quantify weathering rates on rocky desert surfaces. Surface topography on eight late Quaternary alluvial terraces, which record the weathering of Holocene (5 ± 1 ka) boulder-strewn deposits into mature (87 ± 2 ka) desert pavements in the Negev desert of Israel, was measured with ground-based lidar. Roughness on each terrace was characterized with power spectral density (PSD) analysis, and changes in PSD as a function of length scale (λ ∼ 0.04–1.50 m) and surface age were used to estimate diminution/weathering rates of the surface rocks. We found PSD values that systematically increase as a power-law function of λ (roughness exponent of ∼2.0) and decrease as an inverse power-law function of surface age. This PSD evolution indicates a fragmentation rock weathering process driven by salt shattering throughout the 87 k.y. period examined. PSD analysis of the lidar data also revealed weathering rates that increase with rock size and decrease as an inverse power-law function of time, from initial values >20 mm/k.y. to <1 mm/k.y. within ∼60 k.y.


Ocean acidification (OA) is generally assumed to negatively impact calcification rates of marine organisms. At a local scale however, biological activity of macrophytes may generate pH fluctuations with rates of change that are orders of magnitude larger than the long‐term trend predicted for the open ocean. These fluctuations may in turn impact benthic calcifiers in the vicinity. Combining laboratory, mesocosm and field studies, such interactions between OA, the brown alga Fucus vesiculosus, the sea grass Zostera marina and the blue mussel Mytilus edulis were investigated at spatial scales from decimetres to 100s of meters in the western Baltic. Macrophytes increased the overall mean pH of the habitat by up to 0.3 units relative to macrophyte‐free, but otherwise similar, habitats and imposed diurnal pH fluctuations with amplitudes ranging from 0.3 to more than 1 pH unit. These amplitudes and their impact on mussel calcification tended to increase with increasing macrophyte biomass to bulk water ratio. At the laboratory and mesocosm scales, biogenic pH fluctuations allowed mussels to maintain calcification even under acidified conditions by shifting most of their calcification activity into the daytime when biogenic fluctuations caused by macrophyte activity offered temporal refuge from OA stress. In natural habitats with a low biomass to water body ratio, the impact of biogenic pH fluctuations on mean calcification rates of M. edulis was less pronounced. Thus, in dense algae or seagrass habitats, macrophytes may mitigate OA impact on mussel calcification by raising mean pH and providing temporal refuge from acidification stress.


This article takes a new approach to the problem of legal rationality. In the 1920s and 1930s the Legal Realists criticized judicial decisions as "magic solving words" and "word ritual." Though the Realist critique continues to shape American jurisprudence, the legal magic they observed has never been seriously explored. Here, drawing on anthropological studies of magic and ritual, I reconsider the irrational legal techniques the Realists exposed. My thesis is that the Realists were right that law works like magic, but wrong about how magic works. That is, they were right that adjudication makes use of a particular combination of techniques - enacting performances, heightened formality, transformative analogy, performativity, temporal play - that is also found in ritual magic. But they were wrong that those techniques necessarily preclude rational decisionmaking. Drawing on the insights of field anthropology, I theorize legal magic as an authentic mode of legal practice. After considering the different aspects of legal magic and the Realists' critique, I propose three potential roles for legal magic: as a way to imbue official legal decisions with the affective moral force of lived experience, as an institutional practice that may enhance judicial impartiality, and as a method for symbolically reversing otherwise irreparable injuries. I hope that my reanalysis of legal magic can provide a new perspective on the relationship of law and reason, illuminate undertheorized aspects of law and contribute to a more concrete and nuanced understanding of adjudication's social role.


This paper presents a research in progress about an interaction redesign of an educational software based on a new semio-participatory
approach. Brazil is a multicultural country, and its diversity may affect the educational and interactive processes. With the increase of digital technologies use into classroom, the impact of the people culture on interaction with that technologies should be consider. Particular cultural context makes for the people use solely specific signs of their signification systems, ignoring possible signs that are unknown. Based on the Semiotic Engineering and Participatory Design, this study aims to develop a multicultural interaction design approach which support end-users' diversified needs. An action research is adopted to drive an interaction redesign. Using the Semio-participatory approach is expected to be
possible to introduce the cultural and pedagogical characteristics of subject-users on the interface, developing a multicultural interaction.


Procedure-based design is well-established, supporting engineers via expert knowledge codified in resources such as handbooks, tables, and heuristic if-then rules of thumb. These procedures enable even inexperienced designers to benefit from the knowledge obtained by more experienced counterparts through years of practice and discovery. While procedural approaches have many advantages, they do have limitations. They tend to produce only satisficing, rather than optimal, solutions. In addition, they are based on historical designs, so offer little assistance for new system types, and are often descriptive rather than normative in nature. In contrast, normative methods—such as constrained optimization—can resolve many of these issues, but at the cost of significant development effort. Here we present a synergistic hybrid strategy with the objective of capitalizing on established procedure-based design methods for a subset of design problem elements, while incorporating normative strategies for the remaining elements. A design procedure is analyzed to identify steps that involve specification of design variables, and a subset of rule-based steps that could be replaced with optimization algorithms. A single-stage spur gear train design example is used to illustrate this process, and for comparing alternative hybrid solution strategies. Initial results indicate that solution quality can be improved significantly over purely procedurebased design when incorporating limited optimization elements, while maintaining a reasonable level of additional modeling ef-


Anti‐Nogo‐A antibody and chondroitinase ABC (ChABC) enzyme are two promising treatments that promote functional recovery after spinal cord injury (SCI). Treatment with them has encouraged axon regeneration, sprouting and functional recovery in a variety of spinal cord and central nervous system injury models. The two compounds work, in part, through different mechanisms, so it is possible that their effects will be additive. In this study, we used a rat cervical partial SCI model to explore the effectiveness of a combination of anti‐Nogo‐A, ChABC, and rehabilitation. We found that spontaneous recovery of forelimb functions reflects the extent of the lesion on the ipsilateral side. We applied a combination treatment with acutely applied anti‐Nogo‐A antibody followed by delayed ChABC treatment starting at 3 weeks after injury, and rehabilitation starting at 4 weeks, to accommodate the requirement that anti‐Nogo‐A be applied acutely, and that rehabilitation be given after the cessation of anti‐Nogo‐A treatment. We found that single treatment with either anti‐Nogo‐A or ChABC, combined with rehabilitation, produced functional recovery of similar magnitude. The combination treatment, however, was more effective. Both single treatments produced increases in sprouting and axon regeneration, but the combination treatment produced greater increases. Anti‐Nogo‐A stimulated growth of a greater number of axons with a diameter of > 3 μm, whereas ChABC treatment stimulated increased growth of finer axons with varicosities. These results point to different functions of Nogo‐A and chondroitin sulfate proteoglycans in axonal regeneration. The combination of anti‐Nogo‐A, ChABC and rehabilitation shows promise for enhancing functional recovery after SCI.


Trypanosoma cruzi is an organism highly resistant to ionizing radiation. Following a dose of 500 Gy of gamma radiation, the fragmented genomic DNA is gradually reconstructed and the pattern of chromosomal bands is restored in less than 48 hours. Cell growth arrests after irradiation but, while DNA is completely fragmented, RNA maintains its integrity. In this work we compared the transcriptional profiles of irradiated and non-irradiated epimastigotes at different time points after irradiation using microarray. In total, 273 genes were differentially expressed; from these, 160 were up-regulated and 113 down-regulated. We found that genes with predicted functions are the most prevalent in the down-regulated gene category. Translation and protein metabolic processes, as well as generation of precursor of metabolites and energy pathways were affected. In contrast, the up-regulated category was mainly composed of obsolete sequences (which included some genes of the kinetoplast DNA), genes coding for hypothetical proteins, and Retrotransposon Hot Spot genes. Finally, the tyrosyl-DNA phosphodiesterase 1, a gene involved in double-strand DNA break repair process, was up-regulated. Our study demonstrated the peculiar response to ionizing radiation, raising questions about how this organism changes its gene expression to manage such a harmful stress.


1. The changes in plasma volume, haemodynamic variables, plasma renin activity and plasma aldosterone were studied in forty-one hypertensive patients after administration of adrenergic-blocking agents. Four drugs were used: alpha-methyldopa (fourteen patients), guanethidine (ten patients), clonidine (nine patients) and reserpine (eight patients). Drugs were administered orally during 7 days' hospitalization on a normal sodium diet (110 mmol/day). 2. The four drugs had similar effects: a significant decrease in blood pressure, a significant increase in plasma volume and no change in stroke volume. 3. With alpha-methyldopa and guanethidine, heart rate, plasma renin activity and plasma aldosterone were unchanged. 4. With reserpine and clonidine, heart rate and plasma renin activity were significantly decreased, whereas plasma aldosterone did not change significantly. 5. This study suggests that the decrease in plasma renin activity was related to the lowering of the heart rate rather than to sodium retention and that adrenergic-blocking agents can impair the normal relationship between stroke index and plasma volume, between plasma volume and plasma renin activity, and between plasma renin activity and plasma aldosterone.


Abstract. The Grace satellite pair has been in operation since March 2002 providing monthly gravity potential solutions. This data set contains the variation of the gravity potential as a function of time however its use is limited by the presence of vertical striping noise which overwhelms the time variable signal. Several sophisticated filters exist to extract the time variable signal from the noise however they are seldom used as these filters are complex and difficult to implement. Consequently a large proportion of users of time variable Grace data use a conventional Spherical Gaussian Filter with a large smoothing radius of 600–1000 km which greatly attenuates the vertical striping noise however it also attenuates the remaining signal significantly. The difficulty in removing the noise is that the vertical striping noise is not band limited. We have studied the nature of the vertical striping noise and have found that it occurs over all harmonic degrees however it is associated only with the high harmonic orders. We also find that it occurs only in the east–west and radial components of the gravity field and that the noise is much greater than the signal in these two components. Further we observe that these two components are very similar at all geographic latitudes and that by performing a phase shift and subtracting one component from the other, one obtains a noise free signal. We use this procedure to define a new filter which we call the Sawtooth Filter and find that this filter offers three interesting properties: (i) it subtracts the vertical striping noise from the time variable signal (ii) it amplifies the higher degree harmonics thus improving the spatial resolution (iii) it is simpler to implement and use than the Spherical Gaussian Filter.


This paper critically examines a project aimed at improving Indonesian capacity in water and sanitation through a process of institutional strengthening. Funded by the Australian Agency for International Development (AusAID) this involved the partnering of Murdoch University's Environmental Technology Centre (ETC), Australia and Merdeka University's Institute for Environmental Management and Technology (IEMT), Indonesia. Through a series of collaborative activities, the project sought to develop the capacity of IEMT staff to be better able to provide services and training to local government, NGOs, industry and academia on water and sanitation. The project comprised of three phases designed to 1) understand IEMT's existing capacity; 2) identify the needs and priorities of IEMT's stakeholders; and, 3) to further develop IEMT's capacity through the joint implementation of a training-of-trainers workshop. Each of the phases was delivered with some success. However, by means of participant observation, interviews with project members and stakeholders as well as subsequent qualitative analysis the activities were critiqued identifying a number of areas of concern. Foremost, it was concluded that the training-of-trainers model was not appropriate in this context due to inconsistencies with good practice guidelines for capacity building and learning theory. Further, it was established that while the needs were assessed the extent to which they informed decision making was limited. It is suggested that these challenges are not uncommon in capacity building projects of a similar nature. This is due to the fact that the approach employed is often strongly influenced by the experience and expectations of the project members. And, that there is a lack of appropriate training models for use in capacity development from which to draw experience. As such, the resulting training is often the replication of a familiar approach that may do little to develop the capacity of the target audience.


BACKGROUND: Gynecomastia is the most common benign proliferation of the glandular tissue of the male breast and is caused by an alteration of the balance between estrogen and androgen concentrations. In most cases, the treatment of choice is surgery. In this study, we aimed to indicate the efficacy of established surgical procedures for the correction of gynecomastia, as evaluated according to Simon's classification, and to present a novel contribution. METHODS: This study was performed between March 2009 and March 2011. It included 32 male patients, aged between 13 and 45 years. The type of incision was chosen on the basis of the need for skin resection. We used 4 techniques described in the literature and a modified procedure of circular incision with inferior, superior, lateral, and medial extensions, which we employed when excess skin was also present in the lower pole of the breast. RESULTS: Idiopathic gynecomastia was the most common etiology among our patients, followed by obesity and by use of anabolic steroids. CONCLUSIONS: The common procedure to correct gynecomastia was based on the inferior periareolar incision proposed by Webster, which we employed in patients who did not require skin resection. In the presence of excess skin, the technique chosen varied according to the amount of tissue to be resected. In the present report, we propose a novel technique that facilitates larger dermal, glandular, and fatty breast tissue removal when compared to other procedures previously used by this surgeon.


Resonant excited state absorption (ESA) and relaxation processes in Tb(3+)-doped aluminosilicate glasses are quantitatively evaluated. A model describing the excitation steps and upconversion emission is developed and applied to interpret the results from laser-induced surface deformation using thermal mirror spectroscopy. The fluorescence quantum efficiency of level (5)D(4) was found to be close to unity and concentration independent while, for the level (5)D(3), it decreases with Tb(3+) concentration. Emission spectroscopy measurements supported these results. ESA cross sections are found to be more than three orders of magnitude higher than the ground state absorption cross section.


Nonalcoholic fatty liver disease (NAFLD) is a common clinical condition which is associated with metabolic syndrome in 70% of cases. Inappropriate dietary fat intake, excessive intake of soft drinks, insulin resistance and increased oxidative stress combine to increase free fatty acid delivery to the liver, and increased hepatic triglyceride accumulation contributes to fatty liver. Regular soft drinks have high fructose corn syrup which contains basic sugar building blocks, fructose 55% and glucose 45%. Soft drinks are the leading source of added sugar worldwide, and have been linked to obesity, diabetes, and metabolic syndrome. The consumption of soft drinks can increase the prevalence of NAFLD independently of metabolic syndrome. During regular soft drinks consumption, fat accumulates in the liver by the primary effect of fructose which increases lipogenesis, and in the case of diet soft drinks, by the additional contribution of aspartame sweetener and caramel colorant which are rich in advanced glycation end products that potentially increase insulin resistance and inflammation. This review emphasizes some hard facts about soft drinks, reviews fructose metabolism, and explains how fructose contributes to the development of obesity, diabetes, metabolic syndrome, and NAFLD.


Probabilistic Classifiers Chains (PCC) offers interesting properties to solve multi-label classification tasks due to its ability to estimate the joint probability of the labels. However, PCC presents the major drawback of having a high computational cost in the inference process required to predict new samples. Lately, several approaches have been proposed to overcome this issue, including beam search and an e-Approximate algorithm based on uniform-cost search. Surprisingly, the obvious possibility of using heuristic search has not been considered yet. This paper studies this alternative and proposes an admisible heuristic that, applied in combination with A* algorithm, guarantees, not only optimal predictions in terms of subset 0/1 loss, but also that it always explores less nodes than e-Approximate algorithm. In the experiments reported, the number of nodes explored by our method is less than two times the number of labels for all datasets analyzed. But, the difference in explored nodes must be large enough to compensate the overhead of the heuristic in order to improve prediction time. Thus, our proposal may be a good choice for complex multi-label problems.


The renal outer medullary potassium (ROMK) channel is a member of the inwardly rectifying family of potassium (Kir) channels. ROMK (Kir1.1) is predominantly expressed in kidney where it plays a major role in the salt reabsorption process. Loss-of-function mutations in the human Kir1.1 channel are associated with antenatal Bartter's syndrome type II, a life-threatening salt and water balance disorder. Heterozygous carriers of Kir1.1 mutations associated with antenatal Bartter's syndrome have reduced blood pressure and a decreased risk of developing hypertension by age 60. These data suggest that Kir1.1 inhibitors could represent novel diuretics for the treatment of hypertension. Because little is known about the molecular pharmacology of Kir1.1 channels, assays that provide a robust, reliable readout of channel activity-while operating in high-capacity mode-are needed. In the present study, we describe high-capacity, 384- and 1,536-well plate, functional thallium flux, and IonWorks electrophysiology assays for the Kir1.1 channel that fulfill these criteria. In addition, 96-well (86)Rb(+) flux assays were established that can operate in the presence of 100% serum, and can provide an indication of the effect of a serum shift on compound potencies. The ability to grow Madin-Darby canine kidney cells expressing Kir1.1 in Transwell supports provides a polarized cell system that can be used to study the mechanism of Kir1.1 inhibition by different agents. All these functional Kir1.1 assays together can play an important role in supporting different aspects of drug development efforts during lead identification and/or optimization.


Abstract. One seventh of the world's population lives in the Indo-Gangetic Plain (IGP) and the fertile region sustains agricultural food crop production for much of South Asia, yet it remains one of the most under-studied regions of the world in terms of atmospheric composition and chemistry. In particular, the emissions and chemistry of volatile organic compounds (VOCs) that form surface ozone and secondary organic aerosol through photochemical reactions involving nitrogen oxides are not well understood. In this study, ambient levels of VOCs such as methanol, acetone, acetaldehyde, acetonitrile and isoprene were measured for the first time in the IGP. A new atmospheric chemistry facility that combines India's first high-sensitivity proton transfer reaction mass spectrometer, an ambient air quality station and a meteorological station, was used to quantify in situ levels of several VOCs and air pollutants in May 2012 at a suburban site in Mohali (northwest IGP). Westerly winds arriving at high wind speeds (5–20 m s−1) in the pre-monsoon season at the site were conducive for chemical characterization of regional emission signatures. Average levels of VOCs and air pollutants in May~2012 ranged from 1.2 to 2.7 nmol mol−1 for aromatic VOCs, 5.9 to 37.5 nmol mol−1 for the oxygenated VOCs, 1.4 nmol mol−1 for acetonitrile, 1.9 nmol mol−1 for isoprene, 567 nmol mol−1 for carbon monoxide, 57.8 nmol mol−1 for ozone, 11.5 nmol mol−1 for nitrogen oxides, 7.3 nmol mol−1 for sulfur dioxide, 104 μg m−3 for PM2.5 and 276 μg m−3 for PM10. By analyzing the one-minute in situ data with meteorological parameters and applying chemical tracers (e.g., acetonitrile for biomass burning) and inter-VOC correlations, we were able to constrain major emission source activities on both temporal and diel scales. Wheat residue burning caused massive increases (> 3 times the baseline values) for all the measured VOCs and primary pollutants. Other forms of biomass burning at night were also a significant source of oxygenated VOCs and isoprene (r2 with acetonitrile g0.5 for nighttime data), which is remarkable in terms of atmospheric chemistry implications. Surface ozone exceeded the 8 h national ambient air quality limit of 100 μg O3 m−3 (~50 ppbv) on a daily basis, except for 17 May 2012, when a severe dust storm event (PM2.5 > 800 μg m−3; PM10 > 2700 μg m−3) characterized by long-range transport from the west impacted the site. The novel data set and results point to the occurrence of high primary emissions of reactive VOCs. They also highlight the urgent need for establishing more comprehensive observational facilities in the IGP to constrain the spatial and seasonal variability of atmospheric chemical constituents. Such efforts will enable a mechanistic-level understanding of the in situ chemical processes controlling the formation of surface ozone, a necessary step for effective ozone mitigation and improvement of the regional air quality.


Electroencephalography (EEG) based Brain-Computer Interface (BCI) systems are a new development in the field of applied neurophysiology. This new approach has been made possible thanks to progress in EEG analysis and in information technology which has led to a better understanding of psychophysical aspects of the EEG signals. BCI systems enable information flow from the brain directly to the outside world. For widespread use of brain signals for such objectives, effective signal analysis and pattern recognition techniques are needed. In this thesis, we have developed a new technique based on hidden Markov models, and have demonstrated the effectiveness of our algorithms both on a standard dataset and on the data that we have collected in our laboratory. We have used HMMs with AR features combined with PCA to classify two and four class single trial EEG data recorded during imagination of motor actions type of BCI experiments. Results were compared with previous HMM based BCI classifiers and Mahalanobis distance classifier fed with two different state-of-theart EEG features.


This report describes a salvage pathway whereby activated T lymphocytes revert to nonproliferating cells in the absence of antigen or mitogenic signals. After the removal of mitogenic cytokines, cultured T lymphocytes cease dividing and rapidly begin to undergo cell death. However, the addition of fibroblasts to interleukin 2 (IL-2)-propagated T cells results in prolonged survival of the previously activated T lymphocytes in the absence of proliferation. The prevention of cell death is also achieved by conditioned medium from the fibroblasts. T lymphocytes cultured with fibroblasts or the conditioned medium retain the ability to be restimulated if mitogenic stimuli are added to the culture. The activity is not accounted for by IL-1-7. The studies suggest a stromal cell-mediated, nonspecific mechanism for survival of primed T lymphocytes in a nonproliferating state.


Many journalism stakeholders have begun looking to philanthropic foundations to help newsrooms find economic sustainability. The rapidly expanding role of foundations as a revenue source for news publishers raises an important question: How do foundations exercise their influence over the newsrooms they fund? Using the hierarchy of influence model, this study utilizes more than 40 interviews with journalists at digitally native nonprofit news organizations and employees from foundations that fund nonprofit journalism to better understand the impact of foundation funding on journalistic practice. Drawing on previous scholarship exploring extra-media influence on the news industry, we argue that the impact of foundations on journalism parallels that of advertisers throughout the 20th century—with one important distinction: Journalism practitioners and researchers have long forbidden the influence from advertisers on editorial decisions, seeing the blurring of the two as inherently unethical. Outside funding from foundations, on the other hand, is often premised on editorial influence, complicating efforts by journalists to maintain the firewall between news revenue and production.


Residential proxy has emerged as a service gaining popularity recently, in which proxy providers relay their customers' network traffic through millions of proxy peers under their control. We find that many of these proxy peers are mobile devices, whose role in the proxy network can have significant security implications since mobile devices tend to be privacyand resource-sensitive. However, little effort has been made so far to understand the extent of their involvement, not to mention how these devices are recruited by the proxy network and what security and privacy risks they may pose. In this paper, we report the first measurement study on the mobile proxy ecosystem. Our study was made possible by a novel measurement infrastructure, which enabled us to identify proxy providers, to discover proxy SDKs (software development kits), to detect Android proxy apps built upon the proxy SDKs, to harvest proxy IP addresses, and to understand proxy traffic. The information collected through this infrastructure has brought to us new understandings of this ecosystem and important security discoveries. More specifically, 4 proxy providers were found to offer app developers mobile proxy SDKs as a competitive app monetization channel, with $50K per month per 1M MAU (monthly active users). 1,701 Android APKs (belonging to 963 Android apps) turn out to have integrated those proxy SDKs, with most of them available on Google Play with at least 300M installations in total. Furthermore, 48.43% of these APKs are flagged by at least 5 anti-virus engines as malicious, which could explain why 86.60% of the 963 Android apps have been removed from Google Play by Oct 2019. Besides, while these apps display user consent dialogs on traffic relay, our user study indicates that the user consent texts are quite confusing. We even discover a proxy SDK that stealthily relays traffic without showing any notifications. We also captured 625K cellular proxy IPs, along with a set of suspicious activities observed in proxy traffic such as ads fraud. We have reported our findings to affected parties, offered suggestions, and proposed the methodologies to detect proxy apps and proxy traffic. ∗Corresponding author


Ancient speleothems were recovered from caves that today are situated in a high-alpine cirque landscape at 2500 m altitude at the northern rim of the European Alps. U-Pb ages date speleothem deposition to the early Quaternary (between 2.16 and 2.12 Ma and ca. 2.00 Ma), i.e., well before the onset of major alpine and Northern Hemisphere glaciations. Using a stable isotope–based modeling approach, we quantitatively estimate the paleoelevation of both the caves and their former catchment area, which in turn allows us to calculate rates of rock and surface uplift (and hence erosion) since 2 Ma. We show that for the frontal part of the Alps, rates of rock uplift and erosion were ∼0.75 and ∼0.5 mm/yr, respectively, and further suggest that isostatic uplift of mountain peaks of as much as ∼500 m in response to enhanced glacial erosion occurred during the Quaternary. This study highlights the potential of U-Pb-dated speleothems for reconstructing paleoaltimetry, particularly in calcareous mountain ranges, where a standard thermochronologic assessment of exhumation and erosion is generally not feasible.


Metalloporphyrins
are molecules capable of optically sensing targets due to their
specific reactivity. Shifts in metalloporphyrins spectra are usually
in the order of 30 nm, requiring a spectrophotometer for transducing
the analyte concentration. Mesoporous oxide thin films photonic
crystals (PC) act as optical filters, while their pores can host
molecular moieties. In this work used a metalloporphyrin, MnIII
meso-tetra(N-methyl-4-pyridyl) porphyrin (MP), to add a recognition
functionality to a PC and, at the same time, retain their pore
network, in order to develop a versatile and portable sensing device
for volatile amines. The hybrid material MP@PC was prepared by
immersion of the PC, synthesized from two mesoporous oxides with
different refractive index, in an MP solution. The system was
characterized by UV-Vis absorption and FTIR spectroscopies, and SEM
microscopy. Sensing of small molecules was tested using
ethylenediamine (EDA) as a volatile amine model, showing an
absorbance increase in the PC spectral window with promising
analytical parameters. The hybrid material presents enhanced sensing
capabilities compared to MP or PC alone.
A
prototype device was built, aiming for a future design of simple,
low-cost equipment, with a light emitting diode and a light-dependent
resistor, including the MP@PC
sensor.
The device is capable of sensing with only 1.52 μg of MP on a 1 cm2
glass slide and it is easily prepared and showed a very small
detection limit.


We evaluated the effects of protriptyline on snoring characteristics in 14 nonapneic snorers (age range, 23 to 54 years; body mass index, 27.4 +/- 0.9 kg/m2, mean +/- SEM). The study design was a double-blind placebo-controlled crossover trial. Patients were evaluated during a polysomnographic study after each 2 weeks of treatment. Breathing sounds were recorded with two microphones symmetrically placed on each side of the bed, the signal being preamplified, equalized, and analyzed by using a real time analyzer. A snoring event was defined as a breathing sound with a sound pressure level (SPL) greater than 60 dB SPL. The snoring index (number/sleep hour) and the sound intensity of each event were automatically determined. Mild side effects were observed in ten subjects, but no subject interrupted the study because of them. The REM sleep time decreased with protriptyline with a parallel increase in stages 1 to 2. There was no difference in body position during sleep between the placebo and protriptyline trials. The snoring index decreased from 335 +/- 40 with placebo to 238 +/- 41 with protriptyline (p < 0.05) with important individual differences. Among the different sleep stages, the highest values of the snoring index were observed in slow-wave sleep with placebo. The snoring index decreased in each sleep stage with protriptyline, the highest decrease occurring in slow-wave sleep. The percentage of total sleep time (TST) spent above 60 dB SPL was significantly lower with protriptyline (6.1 +/- 1.2 percent TST) than with placebo (8.6 +/- 1.2 percent TST). Changes in snoring characteristics were not correlated with snoring severity, the drug blood level, the body mass index, or the drug-induced modifications in sleep architecture. We conclude that protriptyline can improve both snoring frequency and loudness in some nonapneic snorers, and that this improvement occurs mostly in the sleep stages where snoring is worst.


An integrative taxonomic analysis using color pattern, morphology, and 1449 base pairs of the ND2 mitochondrial gene and its five flanking tRNAs demonstrated that eight species-level lineages occur within the Cyrtodactylus intermedius complex (Cyrtodactylus intermedius sensu stricto, C. phuquocensis and related populations) of the Cardamom mountains and associated highlands that have a sequence divergence ranging 3.4-8.9%. Additionally, each lineage is discretely diagnosable from one another based on morphology and color pattern and most occur in specific geographic regions (upland areas, karst formations or islands) that prevent or greatly restrict interpopulation gene flow. Six of these lineages were masquerading under the nomen C. intermedius and are described as the following: Cyrtodactylus auralensis sp. nov. endemic to Phnom Aural, the highest mountain in Cambodia; C. bokorensis sp. nov. endemic to the Bokor Plateau, Cambodia; C. cardamomensis sp. nov. from the main block of the Cardamom mountains; C. thylacodactylus sp. nov. endemic to Phnom Dalai the northernmost peak of the Cardamom mountains; C. laangensis sp. nov. endemic to the Phnom Laang karst formation, Cambodia; and C. septimontium sp. nov. from the Bảy Núi Hills of southwest Vietnam.


The subject of this Ph.D. research thesis is the development and application of multiplexed analytical methods based on bioluminescent whole-cell biosensors.
One of the main goals of analytical chemistry is multianalyte testing in which two or more analytes are measured simultaneously in a single assay. The advantages of multianalyte testing are work simplification, high throughput, and reduction in the overall cost per test. The availability of multiplexed portable analytical systems is of particular interest for on-field analysis of clinical, environmental or food samples as well as for the drug discovery process. To allow highly sensitive and selective analysis, these devices should combine biospecific molecular recognition with ultrasensitive detection systems. To address the current need for rapid, highly sensitive and inexpensive devices for obtaining more data from each sample,genetically engineered whole-cell biosensors as biospecific recognition element were combined with ultrasensitive bioluminescence detection techniques. Genetically engineered cell-based sensing systems were obtained by introducing into bacterial, yeast or mammalian cells a vector expressing a reporter protein whose expression is controlled by regulatory proteins and promoter sequences. The regulatory protein is able to recognize the presence of the analyte (e.g., compounds with hormone-like activity, heavy metals…) and to consequently activate the expression of the reporter protein that can be readily measured and directly related to the analyte bioavailable concentration in the sample. Bioluminescence represents the ideal detection principle for miniaturized analytical devices and multiplexed assays thanks to high detectability in small sample volumes allowing an accurate signal localization and quantification.
In the first chapter of this dissertation is discussed the obtainment of improved bioluminescent proteins emitting at different wavelenghts, in term of increased thermostability, enhanced emission decay kinetic and spectral resolution. The second chapter is mainly focused on the use of these proteins in the development of whole-cell based assay with improved analytical performance. In particular since the main drawback of whole-cell biosensors is the high variability of their analyte specific response mainly caused by variations in cell viability due to aspecific effects of the sample's matrix, an additional bioluminescent reporter has been introduced to correct the analytical response thus increasing the robustness of the bioassays. The feasibility of using a combination of two or more bioluminescent proteins for obtaining biosensors with internal signal correction or for the simultaneous detection of multiple analytes has been demonstrated by developing a dual reporter yeast based biosensor for androgenic activity measurement and a triple reporter mammalian cell-based biosensor for the simultaneous monitoring of two CYP450 enzymes activation, involved in cholesterol degradation, with the use of two spectrally resolved intracellular luciferases and a secreted luciferase as a control for cells viability.
In the third chapter is presented the development of a portable multianalyte detection system. In order to develop a portable system that can be used also outside the laboratory environment even by non skilled personnel, cells have been immobilized into a new biocompatible and transparent polymeric matrix within a modified clear bottom black 384 -well microtiter plate to obtain a bioluminescent cell array. The cell array was placed in contact with a portable charge-coupled device (CCD) light sensor able to localize and quantify the luminescent signal produced by different bioluminescent whole-cell biosensors. This multiplexed biosensing platform containing whole-cell biosensors was successfully used to measure the overall toxicity of a given sample as well as to obtain dose response curves for heavy metals and to detect hormonal activity in clinical samples (PCT/IB2010/050625: "Portable device based on immobilized cells for the detection of analytes." Michelini E, Roda A, Dolci LS, Mezzanotte L, Cevenini L , 2010). At the end of the dissertation some future development steps are also discussed in order to develop a point of care (POCT) device that combine portability, minimum sample pre-treatment and highly sensitive multiplexed assays in a short assay time. In this POCT perspective, field-flow fractionation (FFF) techniques, in particular gravitational variant (GrFFF) that exploit the earth gravitational field to structure the separation, have been investigated for cells fractionation, characterization and isolation. Thanks to the simplicity of its equipment, amenable to miniaturization, the GrFFF techniques appears to be particularly suited for its implementation in POCT devices and may be used as pre-analytical integrated module to be applied directly to drive target analytes of raw samples to the modules where biospecifc recognition reactions based on ultrasensitive bioluminescence detection occurs, providing an increase in overall analytical output.


Devices such as mobile phones, tablets, wearables, head mounted displays, and computers auto-connect to a wireless network (e.g., a Wi-Fi network) regardless of the speed or quality of the connection offered by the network. In some instances, a Wi-Fi network can deliver lower speed and can be less reliable than a cellular data connection. In such instances, the cellular data connection can be preferable to the Wi-Fi connection. Testing connection speeds of various available connections require connecting to the network first, can cause delays in connection, and requires extra network usage and battery power. This disclosure describes techniques that utilize prior information about the comparative quality of available Wi-Fi and cellular networks, and automatically connects the user device to a preferred network. The prior information includes, e.g., scores for various Wi-Fi networks and expected cellular speed at locations.


Health systems have long been considered key determinants of well-being within modern societies, a valuable resource which have faced a series of reform initiatives throughout the past decades. These reforms have been used to manage the cost of development, measure the tenability of health systems in globalizing economies and promote the increasing importance of health problems related to lifestyle and living conditions, yet they have failed to provide a true resolution to the persistent economical and logistical problems facing modern-day health systems. This rich, interdisciplinary work explores the hypothesis that many of these problems cannot be adequately addressed without structural changes to our health systems, and examines the embedded features of our health systems that underlie contemporary challenges as well as how, and under what conditions, our health systems can be made more sustainable. Combining and building upon theoretical approaches from transition and innovation studies for analysing health system deficits, Toward Sustainable Transitions in Healthcare Systems raises fundamental questions about how new research, new needs and exogenous trends are transforming current health innovation systems. Providing an original and substantial analysis of the complex structural features of the health innovation system, this book will be of interest to students and practitioners of the politics of health, social epidemiology, medical sociology and those with an interest in transition theory.


This paper presents the design, development, and motion control of a novel flexible robotic laparoscope (FRL). The main structure of the FRL includes a two degrees of freedom (DOF) continuum mechanism driven by two pairs of cable-pulley-driven systems, which are actuated by four miniature linear actuators. A constant-curvature model is employed on the kinematics modeling and analysis of the continuum mechanism with designed major arc notches. The bending control strategy of the continuum mechanism is proposed and realized based on its kinematics model and a feedforward compensation method considering its nonlinearity motion calibration with suitable initial tension of the driven cables. Besides, the continuum mechanism is made by elastic nylon material through 3D printing technology. An experimental prototype is developed to test the effectiveness and feasibility of the FRL. The experimental results indicate that the FRL has good positioning accuracy and motion performance with potential applications in robot-assisted laparoscopic surgery.


This report presents evidence-based analysis on Ireland's higher education transformation process towards an innovative, interconnected and multidisciplinary entrepreneurial system, designed to empower its students and staff to demonstrate enterprise, innovation and creativity in teaching, research and societal engagement. Using the OECD-European Commission HEInnovate guidance for the entrepreneurial and innovative higher education institution, the report assesses strategies and practices for entrepreneurship and innovation in Ireland's higher education institutions and the systemic support provided by government.
Higher education institutions play a critical role in Ireland's economy and innovation system, which is based on a strong and growing engagement agenda with industry and local communities, the emergence of new learning environments and strong multidisciplinary research teams. This report offers practical recommendations on how Ireland can enhance and sustain the outcomes.


Traditionally, intelligence was viewed as a single static entity. Revolutionizing the once-dominated "singlestatic entity" conceptualization, Gardner initially (1983) proposed his theory of Multiple intelligences (MI) that encompasses seven different areas of intelligence (verbal-linguistic, logical-mathematical, musical-rhythmic, visual-spatial, bodily-kinesthetic, interpersonal, and intrapersonal), and later on added the eighth and ninth areas (naturalist and existential) in 1999. Based on the theory of Multiple Intelligences (MI), a person may be viewed as intelligent in any of these areas, and the identification of the dominant intelligence type has proven to have pedagogic implications. McKenzie's MI questionnaire (1999) is one of the established tools to identify the typology of intelligence. The present study aims to validate the Persian version of the MI Inventory (questionnaire) proposed by McKenzie (1999). This instrument provides an objective measure of MI. This paper describes the validation exercise of the abovementioned questionnaire that involved 173 pre-university students of both genders in Tehran. In addition, the variables gender and discipline were also considered in this study. The findings of the study indicate that overall, the Persian version of the questionnaire has a high reliability. In addition, the results show a moderate to high relationship between gender and MI profiles of the students.


Nova Scotia's consolidated health system was launched on April 1, 2015. This new approach to organizing health administration and services in the province arose out of necessity. When planning began, Nova Scotia was spending 41% of its annual budget on health services. In comparison to other provinces and territories, our per capita health-related spending was among the highest in the country, we had one of Canada's oldest populations and we had some of the worst health outcomes. Clearly, we could not continue to do the same things and expect different results. Both the life sciences and technology are changing at breakneck speed, while design of healthcare delivery has barely moved beyond a mid-twentieth century paternalistic provider-centric model. Nova Scotia's transformation journey was facilitated by a major policy effort 20 years earlier that had integrated emergency health services across the province. Our aim was to build on that foundation by integrating administration in order to build primary care networks with enhanced regional specialty services, with tertiary services located in Halifax. The goal of health system innovation in Nova Scotia was - and is - based firmly on the dimensions of quality: safe care that avoids harming patients; effective care that is based on levels of evidence to achieve scalability; access to care that is focused on individuals; efficient care that reduces waste, time, energy and supplies; and equitable care that ensures a system is in place that mitigates differences in geography and social economic status. The author offers a sketch of the principal initiatives, challenges, considerations, approaches and lessons involved in this multi-factorial, multi-stakeholder innovation process.


The human glomerular basement membrane belongs to the collagen family of proteins. It contains about 7 percent carbohydrate, half of which occurs as glucosylgalactose disaccharide units linked to hydroxylysine. Glomeruli from diabetics contain increased amounts of basement membrane material. In addition, these membranes show a distict chemical alteration c haracterized by a significant decrease in lysine, accoumpanied by an equivalent increase in hydroxylysine and hydroxylysine-linked disaccharide units.


The authors present the methodology used for collecting data developed through the use of the metaphor of dance. The tools were the workshops run in an Extension Course in Brazil given to nurses caring for women. The process is described as a meeting where the main objective reached was the collective construction of knowledge about the body of the women cared for. The socialization of experiences, the debate of ideas, the reflection about care permeated by solidarity and humanization, caring for the care-givers, reducing the asymmetry between researchers and researched — the dancers — went beyond merely generating data towards research.


We identify experimental signatures in the current-voltage (I-V) characteristics of weakly contacted molecules directly arising from excitations in their many electron spectrum. The current is calculated using a multielectron master equation in the Fock space of an exact diagonalized model many-body Hamiltonian for a prototypical molecule. Using this approach, we explain several nontrivial features in frequently observed I-Vs in terms of a rich spectrum of excitations that may be hard to describe adequately with standard one-electron self-consistent field theories.


OBJECTIVE
To quantitate the potential effectiveness and monetary costs of a policy of elective cesarean delivery for fetal macrosomia diagnosed by ultrasound.

DESIGN
A decision analytic model was constructed to compare 3 policies: (1) management without ultrasound; (2) ultrasound and elective cesarean delivery for estimated fetal weight of 4000 g or more (4000-g policy); and (3) ultrasound and elective cesarean delivery for estimated fetal weight of 4500 g or more (4500-g policy). The impact of maternal diabetes was analyzed separately. Probability data used in the decision analytic model were summarized from the literature and supplemented with unpublished data from the Collaborative Trial of Preterm Birth Prevention. Costs were estimated from the literature, regional reimbursements, and clinical practice data.

MAIN OUTCOME MEASURES
Rates of shoulder dystocia and permanent brachial plexus injury, and both the number of additional cesarean births and monetary costs per permanent brachial plexus injury averted.

RESULTS
In the baseline analysis for nondiabetic women, the ultrasound policies increased both the cesarean delivery rate and costs, while decreasing the rate of shoulder dystocia and brachial plexus injury. For each permanent brachial plexus injury prevented by the 4500-g policy, 3695 cesarean deliveries were performed at an additional cost of $8.7 million, vs 2345 cesarean deliveries and $4.9 million with the 4000-g policy. In the baseline analysis for diabetic women, with all 3 policies, rates of cesarean delivery, shoulder dystocia and brachial plexus injury, and total costs were higher than for nondiabetic women. However, more favorable ratios for both cesarean deliveries and cost per permanent injury avoided were observed: 443 deliveries and $930 000, respectively, with the 4500-g policy, and 489 deliveries and $880 000, respectively, with the 4000-g policy. Sensitivity analysis confirmed the general robustness of these findings.

CONCLUSIONS
For the 97% of pregnant women who are not diabetic, a policy of elective cesarean delivery for ultrasonographically diagnosed fetal macrosomia is medically and economically unsound. In pregnancies complicated by diabetes, such a policy appears to be more tenable, although the merits of such an approach are debatable.


Though transnational labor migration in the Gulf States has increasingly been of scholarly interest, that scholarship has to date relied largely on qualitative ethnographic methodologies or small non-representative sampling strategies. This paper presents the findings of a large representative sample of low-income migrant laborers in Qatar. The data describe the basic characteristics of the low-income migrant population in Qatar, the process by which migrants obtain employment, the frequency with which this population of migrants encounters the problems and challenges described by previous ethnographic work, and the role played by nationality, ethnicity, and religion in patterning that experience. While the findings generally affirm many of the claims made in earlier ethnographic studies, they provide a means by which the extent of these problems and challenges can be ascertained more directly.


The distribution function of local amplitudes, t = \psi(r(0))\(2), of single-particle states in disordered conductors is calculated on the basis of a reduced version of the supersymmetric sigma model solved using the saddle-point method. Although the distribution of relatively small amplitudes can be approximated by the universal Porter-Thomas formulas known from the random-matrix theory, the asymptotical statistics of large t's is strongly modified by localization effects. In particular, we find a multifractal behavior of eigenstates in two-dimensional (2D) conductors which follows from the noninteger power-law scaling for the inverse participation numbers (IPN's) with the size of the system, Vt(n) proportional to L(-(n-1)d*(n)), where d*(n) = 2 - beta(-1)n/(4 pi nu D) is a function of the index n and disorder. The result is valid for all fundamental symmetry classes (unitary, beta(u) = 1; orthogonal, beta(o) = 1/2; symplectic, beta(s) = 2). The multifractality is due to the existence of prelocalized states which are characterized by a power-law form of statistically averaged envelopes of wave functions at the tails, \psi(t)(r)\(2) proportional to r(-2 mu), mu = mu(t) < 1. The prelocalized states in short quasi-one-dimensional (1D) wires have the tails \psi(x)\(2) proportional to x(-2), too, although their IPN's indicate no fractal behavior. The distribution function of the largest-amplitude fluctuations of wave functions in 2D and 3D conductors has logarithmically normal asymptotics.


This study was carried out to determine the effect of adding ginger powder at different levels (0.0, 0.5, 1.0, 2.0%) to the ration on performance, blood parameters and meat quality characteristics of male Japanese quails. 48 male Japanese quail (Coturnix coturnix Japonica) at 28 days of age were used in the study. The experiment was carried out for 21 days in 4 replications in a quail cage with 12 male Japanese quails in each of 4 treatment groups consisting of rations containing different levels of ginger powder. At the end of the experiment, the effects of adding different levels of ginger powder to male quail diets on the performance and serum parameters studied were statistically insignificant. Pre breast L*, a* and b*, thigh meat colours a* and b* values were not significantly affected by the treatments. However, pre-thigh L* values were significantly lower in the group fed with 2.0% ginger powder compared to the group fed with 0.5% and 1.0% ginger powder. Post breast b* value of the group containing 2.0% ginger powder in the diet was significantly higher than that of the group containing 0.5% and 1.0% ginger powder. It was observed the treatment group containing 2.0% ginger powder significantly decreased the pH value and TBA (thiobarbituric acid number) values at the breast meats when compared to the control group and the treatment group containing 0.5% ginger powder. According to the result of the study, it was observed that the addition of ginger powder to male quail rations did not affect performance and serum parameters, but the use of ginger powder at the level of 2.0% in the diet improved some meat quality characteristics.


All visual art must obey the laws of the visual system. The first law is that an image of the visual world is not impressed upon the retina, but assembled together in the visual cortex. Consequently, many of the visual phenomena traditionally attributed to the eye actually occur in the cortex. Among these is visual motion. The second law is that of the functional specialization of the visual cortex, by which we mean that separate attributes of the visual scene are processed in geographically separate parts of the visual cortex, before being combined to give a unified and coherent picture of the visual world. The third law is that the attributes that are separated, and separately processed, in the cerebral cortex are those which have primacy in vision. These are colour, form, motion and, possibly, depth. It follows that motion is an autonomous visual attribute, separately processed and therefore capable of being separately compromised after brain lesions. It is also one of the visual attributes that have primacy, just like form or colour or depth. We conclude that it is this separate visual attribute which those involved in kinetic art have tried to exploit, instinctively and physiologically, from which it follows that in their explorations artists are unknowingly exploring the organization of the visual brain though with techniques unique to them.


This paper analyzes a monopolist's behavior when consumers cannot observe the production standards. These types of products are usually known as credence goods. The steady-state level of quality with credence goods is found to be lower than that with experience goods, and perfect information goods. The finding that only perceived quality, which is effectively a filtered version of true quality, affects reputation indicates rewards for high quality production are lower in the credence good case. Further, an increase in the level of monitoring can increase the true level of product quality in the market for credence goods.


Schizophrenia is a debilitating mental illness which is complex and multifactorial in nature. Currently a full understanding of the exact aetiological and treatment pathways is yet to be understood, with effective treatment of the debilitating and pervasive negative symptoms particularly lacking. However recent advances in neurophysiological and neuropsychological research seem to be converging on theories of the central role of lateralised functional systems. These models implicate right hemispheric hyperactivation in negative symptom patterns, while positive symptoms are thought to be associated with left frontal hypoactivation resulting in compensatory left temporal hyperactivation. Through the use of the Cognitive Neuropsychological case study methodology, this research took an inductive and exploratory approach to a unique case of 41 year old monozygotic twins concordant for schizophrenia and discordant for a right frontal cerebrovascular accident (CVA). From various records the CVA seemingly had a positive effect on the affected-twin's negative symptoms. By means of a selected battery of neuropsychological tests this research focused on patterns of test performance for known functional systems and identified neuropsychological correlates of the CVA and the negative symptom improvement. Statistically significant differences were found between the twins, particularly in the right medial and ventral prefrontal areas. These areas, with their projections to the limbic system and other sub-cortical structures, were highlighted as being important to these differences. From these findings working hypotheses regarding specific lobal structures, relating to existing theories and research in schizophrenia, were posited for future research.


Increasing evidence suggests mammalian Argonaute (Ago) proteins partition into distinct complexes within cells, but there is still little biochemical or functional understanding of the miRNAs differentially associated with these complexes. In naive T cells, Ago2 is found almost exclusively in low molecular weight (LMW) complexes which are associated with miRNAs but not their target mRNAs. Upon T cell activation a proportion of these Ago2 complexes move into a newly formed high molecular weight (HMW) RNA-induced silencing complex (RISC) which is characterized by the presence of the GW182 protein that mediates translational repression. Here we demonstrate distinct partitioning of miRNAs and isomiRs in LMW versus HMW RISCs upon antigen-mediated activation of CD8+ T cells. We identify miR-7 as highly enriched in HMW RISC and demonstrate that miR-7 inhibition leads to increased production of IL-2 and up-regulation of the IL-2 receptor, the transferrin receptor, CD71 and the amino acid transporter, CD98. Our data support a model where recruitment of miR-7 to HMW RISC restrains IL-2 signaling and the metabolic processes regulated by IL-2.


This paper describes a study conducted at the Faculty of Continuing Education, The University of Calgary, that examined the use of two different computer-assisted career guidance systems (SIGI PLUS and CAREER BUILDER2) with a small group (n=40) of adult learners. The results indicate that both systems significantly increased participants' sense of vocational identity, and that SIGI PLUS was somewhat more effective in this regard than CAREER BUILDER2. Implications for the use of this kind of career service with adult continuing education students are discussed.


11 children with either cystinosis or Lowe's syndrome had a reduced content of plasma and muscle carnitine due to renal Fanconi syndrome. After treatment with oral L-carnitine, 100 mg/kg per d divided every 6 h, plasma carnitine concentrations became normal in all subjects within 2 d. Initial plasma free fatty acid concentrations, inversely related to free carnitine concentrations, were reduced after 7-20 mo of carnitine therapy. Muscle lipid accumulation, which varied directly with duration of carnitine deficiency (r = 0.73), improved significantly in three of seven rebiopsied patients after carnitine therapy. One Lowe's syndrome patient achieved a normal muscle carnitine level after therapy. Muscle carnitine levels remained low in all cystinosis patients, even though cystinotic muscle cells in culture took up L-[3H]carnitine normally. The half-life of plasma carnitine for cystinotic children given a single oral dose approximated 6.3 h; 14% of ingested L-carnitine was excreted within 24 h. Studies in a uremic patient with cystinosis showed that her plasma carnitine was in equilibrium with some larger compartment and may have been maintained by release of carnitine from the muscle during dialysis. Because oral L-carnitine corrects plasma carnitine deficiency, lowers plasma free fatty acid concentrations, and reverses muscle lipid accumulation in some patients, its use as therapy in renal Fanconi syndrome should be considered. However, its efficacy in restoring muscle carnitine to normal, and the optimal dosage regimen, have yet to be determined.


Collateral circulation in the brain is important for maintaining a sufficient cerebral blood flow in case of obstructive disease of arteries. In case of hemodynamic compromise to the anterior circulation, the posterior circulation supplies the anterior circulation via the collaterals. Simultaneous anterior and posterior circulation stroke is a very rare occurrence. It can occur due to cardioembolic stroke or due to anatomical variants of the circle of Willis. Fetal origin of the posterior cerebral artery (PCA) from the internal carotid artery (ICA), persistent trigeminal artery, and persistent hypoglossal artery are known to present with posterior circulation stroke due to occlusive disease of ICA. Here we report a 85-year-old man who presented to us with left hemiparesis. On evaluation, he had right middle cerebral artery (MCA), anterior cerebral artery (ACA), and PCA infarct. Our case most likely had fetal PCA, which can readily explain the PCA infarction in ICA occlusion. Although cases of simultaneous MCA and PCA infarction had been reported in past, we report the first case with simultaneous ACA, MCA, and PCA infarction secondary to fetal PCA.


ABSTRACT:This essay raises questions about ways in which law and the interpretive humanities might intersect in such manner as to offer real insight one to another. Specifically, it addresses the use of narrative in the law, and its analytic study. Stories, I argue, are not events in the world, but the way we tell events, a crucial distinction sometimes unrecognized in legal opinions. Examples analyzed include the doctrine of "inevitable discovery" articulated by the Supreme Court in Nix v. Williams, juxtaposed to the creation of a seeming inevitability in the stories of Sherlock Holmes. These issues are further clarified through a discussion of historian Carlo Ginzburg's reflections on the "huntsman's paradigm" and the workings of "retrospective prophecy." The essay then turns more closely to the analysis of narrative, particularly the end-determined nature of narrative meaning, and to the one Supreme Court case I am aware of that discusses narrative in an analytic way: Justice Souter's opinion in Old Chief v. U.S. Further examples are drawn from rape adjudication (Rusk v. Maryland) and post-conviction petitions for relief (Mickens v. Taylor). If narrative, telling the facts, plays so important a role in law, shouldn't the law arm itself with more tools in the analysis of narrative? The notion of law as language, including its grammar and its rhetoric, deserves a place in legal study.


Performance critical software is almost always developed in C, as programmers do not trust high-level languages to deliver the same reliable performance. This is bad because low-level code in unsafe languages attracts security vulnerabilities and because development is far less productive, with PL advances mostly lost on programmers operating under tight performance constraints. High-level languages provide memory safety out of the box, but they are deemed too slow and unpredictable for serious system software. Recent years have seen a surge in staging and generative programming: the key idea is to use high-level languages and their abstraction power as glorified macro systems to compose code fragments in first-order, potentially domain-specific, intermediate languages, from which fast C can be emitted. But what about security? Since the end result is still C code, the safety guarantees of the high-level host language are lost. In this paper, we extend this generative approach to emit ACSL specifications along with C code. We demonstrate that staging achieves ``abstraction without regret'' for verification: we show how high-level programming models, in particular higher-order composable contracts from dynamic languages, can be used at generation time to compose and generate first-order specifications that can be statically checked by existing tools. We also show how type classes can automatically attach invariants to data types, reducing the need for repetitive manual annotations. We evaluate our system on several case studies that varyingly exercise verification of memory safety, overflow safety, and functional correctness. We feature an HTTP parser that is (1) fast (2) high-level: implemented using staged parser combinators (3) secure: with verified memory safety. This result is significant, as input parsing is a key attack vector, and vulnerabilities related to HTTP parsing have been documented in all widely-used web servers.


The transforming events that lead to B-cell chronic lymphocytic leukemia (B-CLL) are unknown, and although genetic abnormalities appear to promote disease progression, none of these is seen in every patient. Therefore, we have applied a highly sensitive and specific method to probe, in greater depth, for genetic changes that can occur in B-CLL, and to explore if these correlate with disease development or progression. Utilizing ROMA to measure changes in gene copy number, we screened the entire genome of over two dozen B-CLL cases to identify characteristic and novel chromosomal changes. DNA from leukemic cells of patients was compared to the normal DNA from their unaffected neutrophils and to an unrelated, normal human control. By comparing normal DNA from each patient to an unrelated normal, we avoid inadvertently mistaking common copy number variation between people as possible candidates for lesions in B-CLL. ROMA was performed on both 85,000 and 390,000 probe microarrays enabling us to screen for far smaller lesions than are detectable by routine techniques, as well as resolve regions of interest, possibly pinpointing important genes in the etiology and progression of B-CLL. Data were also obtained by using the Illumina platform. These two methods (ROMA and Illumina), while not identical, are largely in agreement. We have observed virtually all the major cytogenetic imbalances previously reported, and in many cases to a higher resolution. Although there are fewer lesions present in B-CLL than in more advanced stages of solid cancers, many early stage cancers exhibit only a few common lesions. The most frequent deletion and often the sole abnormality found in B-CLL occurs at chromosome 13q13.4. Two micro-RNAs, miR-15a and miR-16-1, have been implicated in the smallest region of this deletion. ROMA analysis has further delineated the deletions on 13q, suggesting that there may be two epicenters, one encompassing these micro-RNA genes and one encompassing a neighboring region that does not span miR-15a or miR-16-1. A novel finding is the existence in certain patients (5/26) of numerous single probe deletions or amplifications. Since we compare B-CLL to the normal DNA from the same patient, and to a known control, even single probe events can be relevant. Many B-CLLs display single probe aberrations and these events are currently under investigation. In addition, we have observed two patients with major genomic instability, as evidenced by large and multiple regions that change copy number. The analysis of large numbers of B-CLL cases is essential to identifying and understanding the ongoing progression of genetic lesions and the role they play in clinical outcome. Initial results clearly indicate the need to obtain more data to identify critically mutated genes within the leukemic cells that cause them to become more aggressive. The identification and characterization of these genetic changes may be used as stratification tools for new diagnostic and therapeutic approaches to this currently incurable disease.


An important contribution to the scholarship linking literature and technology, Reading Matters offers a sweeping overview of the myriad ways machinery has affected the creation and interpretation of narrative. With topics ranging from how the advent of typewriting divorced the hand from the pen (and so the body from the text) to the appropriation of the conventions of high modernism in the bestselling techno-thriller, this compilation of twelve original essays and a newly translated one examines the authors and the theoretical concerns that have both helped to make prose fiction a marginalized genre and guaranteed its indispensability in our arguably post-chironic cyber age.


The effect of soil frost on runoff was investigated using a comprehensive data set collected at the Svartberget Experimental Forest, near Vindeln, Västerbotten in northern Sweden. Measurements of snow depth, soil temperature, frost depth and other climate parameters have been made at three sites since 1981, as part of a long‐term climate monitoring programme. Simulation residuals from the HBV rainfall–runoff model, in which no effect of soil frost is assumed, were compared with 16 years of measured soil frost conditions. A simple model for simulation of soil frost depth was developed and incorporated into the HBV model. The model parameters were calibrated to observations of snow depth, soil frost depth, groundwater levels and runoff, by use of a simple weighted optimization criterion. No clear effect of soil frost could be seen on the timing and magnitude of runoff in this analysis, or when analysing data on the conservative oxygen isotope 18O. The soil at the forested site froze in only slightly more than half the years, despite the high latitude and low winter temperatures. Furthermore, the soil had often thawed before the start of the spring flood. Almost all spring floods, therefore, occurred when the soil was unfrozen. Snow depth and soil frost depths were inversely related, with the deepest soil frost during winters with little snow. Soil frost therefore is unlikely to aggravate the very high floods in forested basins of this type, except perhaps under exceptional circumstances such as large rain events on frozen ground. Copyright © 2002 John Wiley & Sons, Ltd.