New data for the isotopic composition of carbon in carbonate sediments deposited between 2.6 and 1.6 Ga indicate that the value of δ13C in these sediments underwent a very large positive excursion between 2.22 and 2.06 Ga. A reassessment of the earlier δ13C data for carbonate sediments shows that this excursion was probably worldwide, and that it was preceded and followed by several hundred million years during which the δ13C of carbonate sediments differed little from that of modern carbonates. The large δ13C excursion between 2.22 and 2.06 Ga was probably related to an abnormally high rate of organic carbon deposition, which generated an abnormally high rate of O2 production. We estimate that the total excess O2 produced during the excursion was between 12 and 22 times the present atmospheric O2 inventory. The δ13C data therefore suggest that the O2 content of the atmosphere increased very significantly between 2.22 and 2.06 Ga. This inference is supported strongly by several other lines of evidence.


Several computer-based learning support systems and methods help learners to master metacognitive activity. Which systems and methods are designed to eliminate which difficulties associated with the learning of metacognitive activity through its clear specification? We adopt a method in our research that supports learning by eliminating salient difficulties. We believe that it is possible to eliminate or decrease them through appropriate design only after specifying those difficulties associated with learning. In this study, we analyze difficulties in performing cognitive activity, distinguish factors of difficulty from other factors, and construct our framework, which represents difficulties in performing metacognitive activity. Finally, we organize existing support systems and methods based on that framework.


The PR domain, first noted as thePRDI-BF1-RIZ1 homologous region, defines a sub-class of zinc finger genes that appear to function as negative regulators of tumorigenesis. This family includes the MDS1-EVI1 gene inactivated in myeloid leukemia, the PRDI-BF1/BLIMP1transcription repressor of c-myc involved in driving B-cell differentiation, and the RIZ gene, which encodes proteins capable of binding to the retinoblastoma tumor suppressor protein (Rb). The PR domain of MDS1-EVI1 is disrupted by translocations linked to myeloid leukemia, resulting in the activation of the PR-minus oncogenic product EVI1. Remarkably similar to MDS1-EVI1,RIZ gene also normally produces two protein products of different length, and the smaller protein RIZ2 lacks the PR domain of RIZ1 but is otherwise identical to RIZ1. These observations raise considerable interest to determine the function of PR. We show here that RIZ1 PR domain mediates protein-protein interaction. Recombinant fusion proteins of PR can bind to in vitro translated RIZ1 and RIZ2 proteins. The binding can be disrupted by amino acid substitutions at conserved residues of PR, suggesting that binding is specific. Of the three conserved exons of PR, the first two appear dispensable for binding, whereas the third exon is required. A region in the carboxyl terminus of RIZ proteins was mapped to be necessary and sufficient for PR binding. We also found that the PR domain shares significant sequence identity to the SET domain present in chromosomal proteins that function in modulating gene expression from yeast to mammals. Our data suggest that the PR domain is a derivative of SET domain and may function as protein binding interface in the regulation of chromatin-mediated gene expression.


The data on which this paper is based were collected in and around Salisbury, Southern Rhodesia, during the latter part of 1957 and early 1958 whilst carrying out a preliminary study of Colias electo (L.) as part of an investigation into the insects associated with lucerne. In addition to laboratory and insectary study of the life history of the species, observations were made in a small field of recently-planted lucerne about 18 miles from Salisbury. Descriptions of the stages of C. electo have been given by van Son (1949), Jarvis (1953) and Pinhey (1949) and so are not included in the present paper.


Latinos currently represent the largest minority in the United States. In 2009, we witnessed the first Latina appointment to the United States Supreme Court. Despite these events, Latinos continue to endure racial discrimination and social marginalization in the United States. The inability of Latinos to gain political acceptance and legitimacy in the United States can be attributed to the social construct of Latinos as threats to national security and the cause of criminal activity. Exploiting this pretense, American government, society and nationalists are able to legitimize the subordination and social marginalization of Latinos, specifically Mexicans and Central Americans, much to the detriment of the Latino community. This poisonous social construct has many manifestations – it depicts the Latino as a foreigner, a criminal, an "illegal" and it characterizes the Latino as one who comes to this country to cause social chaos by refusing to follow our country's laws, work with authority, or enter with right. These depictions and characterizations instill fear and contempt against the Latino and motivate the creation of harsh immigration laws and enforcement measures. Ironically, these depictions and characterizations are then used as the pretext for legal actions against the Latino community. Currently, the primary vehicle for accomplishing this disguised discrimination has been the incorporation of immigration law into the criminal justice system. Under the pretext of addressing criminal activity and national security concerns, American law-makers and society use immigration and criminal law to preserve racial inequality and perpetuate the marginalization of Latinos living in the United States. Thus far, these measures have been effective in depriving Latinos of the right to live in this country with rights equal to the majority, and denying them the freedom and privilege of living in the United States without abuse, discrimination, or fear. This Article will discuss the use of the criminal justice system as the current primary means to stigmatize, punish and remove Latinos, the fallacy of the justifications put forth for this discrimination, and the impact of this governmental course of action on the Latino community. This Article concludes that until the Latino identity is disaggregated from the criminal and immigration contexts, discrimination against all Latinos will persist in a state-sanctioned, society approved and formidable form.


Estate settlement through probate procedures satisfies no one. The public is hostile to the delay, expense, and lack of privacy that accompanies probate. Attorneys respond to public dissatisfaction by counseling probate avoidance. Legislatures facilitate some settlements by enacting simplified procedures for low-value estates. In large measure, the Uniform Probate Code (UPC) was a response to criticisms leveled at probate. Alternative settlement procedures are offered by the UPC, including informal testacy determinations and informal appointment procedures. These alternatives, however, remain imbedded in a judicial system, with it procedural rigidities. The UPC informal settlement alternatives did not silence the criticism. The continued dissatisfaction with probate continues to breed devices to avoid probate and shortcut options for small estates. To address the ongoing hostility, this Article advocates the UPC adopt an optional, non-judicial registration system for estate settlement. Patterned after small-estate statutes, a registration system establishes the decedent's testate or intestate status by registering the will or an affidavit of heirship, identifies a personal representative when one is needed, and permits completion of settlement as rapidly as the unique circumstances of each estate permit. A registration system is designed for the majority of estates, the ones that involve no controversy. Utilizing a registration system, the decedent's beneficiaries may collect assets, pay debts, and make distribution promptly, with reduced expense, and without the publicity that judicial proceedings entail. A registration system would be a continuation of the UPC's intent to offer estate settlement modes that are both acceptable to the public and responsive to the purposes of estate settlement.


The environmental culture (EC) is the total learned behaviour, attitudes, practices and knowledge for the society with respect to maintaining or protecting its natural resources. The development of EC is associated primarily with environmental education, awareness, ethics, and training of employees inside and peoples outside of oil and gas industry operations. EC is considered as a specific element, because it influences on decisions about dealing with environmental problems or accidents. The procedure of inserting EC into an environmental management system (EMS) results in more effective environmental protection management and related problems solving. The oil and gas industry operations are series of functions of cementing, acidizing, stimulation, nitrogen services, coiled tubing, fracturing, filtration, grouting, cleaning, oil recovery, maintenance, transporting, and chemical with mechanical treatment. As a new topic, EC is defined as a new element, and the procedure of inserting EC into EMS can be done for improved environmental protection, resulting in an efficient EMS for oil and gas industry operations. The most reputable national and international organizations (such as EMAS, BS 7750, GEM1, and IS0 14000 series) do not refer to EC – they did not enter it into their programs because there is a gap in their contents. As a tactic, inserting EC can achieve the same 17 elements created by International Standards (ISO 14001) and the Environmental Protection Agency (EPA) for gaining results of better outcomes for environmental protection.


(a) In conducting the performance tests required in § 60.8, the owner or operator shall use as reference methods and procedures the test methods in appendix A of this part or other methods and procedures as specified in this section, except as provided in § 60.8(b). (b) The owner or operator shall determine complance with the particulate matter standards § 60.382 as follows: (1) Method 5 or 17 shall be used to determine the particulate matter concentration. The sample volume for each run shall be at least 1.70 dscm (60 dscf). The sampling probe and filter holder of Method 5 may be operated without heaters if the gas stream being sampled is at ambient temperature. For gas streams above ambient temperature, the Method 5 sampling train shall be operated with a probe and filter temperature slightly above the effluent temperature (up to a maximum filter temperature of 121 °C (250 °F)) in order to prevent water condensation on the filter. (2) Method 9 and the procedures in § 60.11 shall be used to determine opacity from stack emissions and process fugitive emissions. The observer shall read opacity only when emissions are clearly identified as emanating solely from the affected facility being observed. A single visible emission observer may conduct visible emission observations for up to three fugitive, stack, or vent emission points within a 15-second interval. This option is subject to the following limitations: (i) No more than three emission points are read concurrently; (ii) All three emission points must be within a 70° viewing sector or angle in front of the observer such that the proper sun position can be maintained for all three points; and (iii) If an opacity reading for any one of the three emission points is within 5 percent opacity of the application standard, then the observer must stop taking readings for the other two points and continue reading just that single point. (c) To comply with § 60.385(c), the owner or operator shall use the monitoring devices in § 60.384(a) and (b) to determine the pressure loss of the gas stream through the scrubber and scrubbing liquid flow rate at any time during each particulate matter run, and the average of the three determinations shall be computed.


Nikolai Ivanovich Vavilov proposed theories of plant genetic diversity and participated in the political debate about genetics in Russia in the early twentieth century. Vavilov collected plant species around the world, building one of the first and most comprehensive seed banks, and he spent much of his life researching plant breeding and genetics. Vavilov also developed a theory of the historical centers of origin of cultivated plants. Vavilov spent most of his scientific career in Russia, although he studied abroad and traveled extensively. The ascent of geneticist Trofim Lysenko, favored by Joseph Stalin, and Vavilov's public criticism of Lysenko lead to Vavilov's arrest in 1940 and his death in prison three years later.


Community structures of active bacterial populations were investigated along a vertical redox profile in coastal Baltic Sea sediments by terminal-restriction fragment length polymorphism (T-RFLP) and clone library analysis. According to correspondence analysis of T-RFLP results and sequencing of cloned 16S rRNA genes, the microbial community structures at three redox depths (179, -64 and -337 mV) differed significantly. The bacterial communities in the community DNA differed from those in bromodeoxyuridine (BrdU)-labelled DNA, indicating that the growing members of the community that incorporated BrdU were not necessarily the most dominant members. The structures of the actively growing bacterial communities were most strongly correlated to organic carbon followed by total nitrogen and redox potentials. Bacterial identification by sequencing of 16S rRNA genes from clones of BrdU-labelled DNA and DNA from reverse transcription polymerase chain reaction showed that bacterial taxa involved in nitrogen and sulfur cycling were metabolically active along the redox profiles. Several sequences had low similarities to previously detected sequences, indicating that novel lineages of bacteria are present in Baltic Sea sediments. Also, a high number of different 16S rRNA gene sequences representing different phyla were detected at all sampling depths.


During the Mesozoic, Crocodylomorpha had a much higher taxonomic and morphological diversity than today. Members of one particularly successful clade, Thalattosuchia, are well‐known for being longirostrine: having long, slender snouts. It has generally been assumed that Thalattosuchia owed their success in part to the evolution of longirostry, leading to a feeding ecology similar to that of the living Indian gharial, Gavialis. Here, we compare form and function of the skulls of the thalattosuchian Pelagosaurus and Gavialis using digital reconstructions of the skull musculoskeletal anatomy and finite element models to show that they had different jaw muscle arrangements and biomechanical behaviour. Additionally, the relevance of feeding‐related mandibular traits linked to longirostry in the radiation of crocodylomorph clades was investigated by conducting an evolutionary rates analysis under the variable rates model. We find that, even though Pelagosaurus and Gavialis share similar patterns of stress distribution in their skulls, the former had lower mechanical resistance. This suggests that compared to Gavialis, Pelagosaurus was unable to process large, mechanically less tractable prey, instead operating as a specialized piscivore that fed on softer and smaller prey. Secondly, innovation of feeding strategies was achieved by rate acceleration of functional characters of the mandible, a key mechanism for the diversification of certain clades like thalattosuchians and eusuchians. Different rates of functional evolution suggest divergent diversification dynamics between teleosaurids and metriorhynchids in the Jurassic.


Even though many water utilities in the United States perform some form of water meter testing, little has been published concerning utility meter accuracy–testing procedures. Although AWWA's Manual M6, Water Meters—Selection, Installation, Testing, and Maintenance (2012), provides much useful information concerning accuracy‐testing principles, the recent development of static residential water meters has introduced new questions about accuracy‐testing procedures that are not addressed in the current edition of M6. This article discusses the results of a study performed at the Utah Water Research Laboratory (UWRL) that involved sending a set of meters to various utility meter shops around the country to be tested. The UWRL tested the meters both before and after the tests were performed at each utility. Each utility forwarded a copy of its accuracy test results to the UWRL, and the results from each utility were then compared with the UWRL test results.


This article reconstructs debates within the Kennedy and Johnson administrations regarding the management of U.S. public transportation. Should transit be treated as a component of the mobility system, or as a tool of land-use planning? In the midst of jurisdictional battles triggered by the formation of two new departments, officials fiercely disagreed about this question and adapted their practices to gain the upper hand. I document how interest in organizing metropolitan growth and concerns about destructive road projects helped justify national housing agencies managing transit programs beginning in 1961. But Congress shifted them to the Department of Transportation in 1968. This was due, I argue, to lingering racist, anti-urban sentiments about housing-agency programs benefiting low-income people and transportation officials previously focused on highways devoting newfound attention to multimodal projects. Despite a fleeting moment of attention to regional land-use and transportation policy, this change ultimately bifurcated and diminished federal planning oversight.


Autophagy has become one of the most attractive topics in cancer due to its dual role as a tumor suppressor and cell survival mechanism that can promote the growth of established tumors. Autophagy (macroautophagy) is an evolutionary protected lysosomal pathway for degrading cytoplasmic proteins, macromolecules, and organelles. Reduction in autophagic capacity or defective autophagy provides an oncogenic stimulus, causing malignant transformation and spontaneous tumors. In addition, autophagy seems to function as a protective cell-survival mechanism against environmental and cellular stress (e.g., nutrient deprivation, hypoxia, and therapeutic stress). Removing damaged organelles under stress conditions improves the survival of cells and causes resistance to antineoplastic therapies, thus leading to hypothesis that the inhibition of autophagy in cancer cells may be therapeutically beneficial in some circumstances, including DNA-damaging agents, antihormone therapies (e.g., tamoxifen), and radiation therapy. Understanding the molecular mechanism regulating autophagy will provide the impetus for translational studies that may ultimately lead to new therapeutic strategies in cancer. The main focus of this special issue will be on the new, and existing, information on the promising agents that inhibit autophagy or induce autophagic cell death, alone or in combination with current standard therapies or experimental therapeutics. This special issue will also explore novel molecular mechanism regulating autophagy and provide the cellular mechanisms for differentiation and cell survival mechanisms in various cancers. Potential topics include, but are not limited to:

Pro- and antiautophagic signaling pathways in normal and cancer cells
Starvation and growth factor deprivation-induced signaling in induction of autophagy
Hypoxia, metabolic stress, and ROS in induction of autophagy
Identification of markers to monitor autophagy in tumors in vivo models and patient samples
Polyphenolic compounds, antioxidants, and small molecules as autophagy/autophagic cell death inducers
Molecularly targeted therapies interfering in autophagy as a potential novel therapeutic strategy in vitro and in vivo cancer models
Clinical studies examining autophagy in patient tumors and its relation with prognosis, survival, and response to therapies


We report from on-going research of 'SMS Chatter ', the largest SMS-based mobile social networking site in India. The aim of this position paper is to share initial results from an investigation of the platform and note its emerging nature and the content of messaging. Unlike other social networking sites like Twitter where conversation, retweeting and maintaining a personalized profile take prominence, mobile social media in India shows different kinds of appropriation. SMS Chatter, seemingly, is not only for 'egocentric' users, but also for individuals and small and medium enterprises that choose the platform to promote various products and services. Posts that are not promotional take the form of short poetry, jokes or inspirational messages and constitute secondary content that is circulated without attribution. In this paper, we will emphasize and delineate two features of SMS Chatter, namely, a) the entwined and informal nature of social and business networking and b) the dominance of borrowed or secondary content of posts and the lack of conversational content or retweets.


ABSTRACT Science requires the acquisition and analysis of empirical (sense-derived) data. Given the same physical objects or phenomena, the sense organs of all people do not respond equally to these stimuli, nor do their minds interpret sensory signals identically. Therefore, teachers should develop lectures on human sensory systems that include some common examples of sensory limitations, variations, deficiencies, malfunctions, and diseases (as discussed herein) because they have important implications for conducting scientific investigations, science education, and introspection that are seldom included in biology textbooks. Students need to be made aware of the human tendency to self deception in order to avoid the cognitive error of confirmation bias.


This thesis will explore how South African portrait and documentary photography produced between 1994 and 2004 has contributed to a wider understanding of the country's painful past and, for some, hopeful, for others, bleak present. In particular, it will examine two South African photographic works which are paradigmatic of the political and social changes that marked the first decade after the fall of apartheid, focusing on the empowerment of both photographers and subjects. The first, Jillian Edelstein's (2001) Truth & Lies: Stories from the Truth and Reconciliation Commission in South Africa, captures the faces and records the stories of perpetrators and victims who gave their testimonies to the Truth and Reconciliation Commission in South Africa from 1996 to 2000. The second, Adam Broomberg and Oliver Chanarin's (2004a) Mr. Mkhize's Portrait & Other Stories from the New South Africa, documents the changed/ unchanged realities of a democratic country ten years after apartheid.

The work of these photographers is showcased for its specificity, historicity and uniqueness. In both works the images are charged with emotion. Viewed on their own — uncaptioned — the photographs have the capacity to unsettle the viewer, but in both cases a compelling intermeshing of image and text heightens their resonance and enables further possibilities for interpretation. In their contributions to the critical theory of photography Roland Barthes, Victor Burgin and Max Kozloff underscore the centrality of the interplay between image and text in the meaning-making process anchoring a critical engagement with photography. Burgin (1982) states that "Even the uncaptioned photograph, framed and isolated on a gallery, is invaded by language when it is looked at", and Kozloff (1987) claims that "However they are perceived, images have to be mediated by words".

This thesis singles out emotionally charged and forceful photographs in Edelstein, Broomberg and Chanarin's repertoire to consider both the complex process of the construction and interpretation of photographic meaning and question if/when photographs do, in fact, depend on language. Central to the architecture of photography is the layering of the representations, firstly through the specific photographic language and form of address which characterises the portrait genre, and secondly through the verbal text accompanying the images. I argue that the viewer's experience of the photograph unfolds at two distinct moments of viewing. The first moment is defined by the "raw" encounter with the photograph — mediated by an affective response to its emotional or symbolic content — and the second moment encompasses the response to the photograph's compositional elements, or signifying units, in articulation with the text/narrative accompanying it.

This analysis brings to the fore the relation and exchange between photographer and subject and, ultimately, between photographer, subject and viewer. Emmanuel Levinas and Hannah Arendt's theoretical insights provide a platform for exploring the lived, concrete experience of ethical choice and action at the core of the photographer–subject-viewer humanistic triangulated relationship. Germane to this discussion, Ariella Azoulay's (2008) conception of "the civil contract of photography" extends the possibility of questioning and/or examining, firstly, the complex intertwining roles of the several participants in the photographic act/encounter and, secondly, the photographic image as an intercultural nexus wherein photographer, subject and viewer meet.
The triangulation of photographer-subject-viewer, which constitutes the guiding thread of this study, is further explored and illuminated from the perspective of Mikhail Bakhtin's conceptualisation of the "utterance", enabling me to engage with the dialogical dimension of photographic practice. The affinities between Levinas and Bakhtin — two philosophers of alterity — revealed through a common language of responsibility in the relation with the other, inform my reading and discussion of the ethical project of photography in post-apartheid South Africa.

Phenomenology, narrative theory and social semiotic visual analysis guide the methodology adopted in this study, creating a synergy between a reflective/dialogical, a discursive/sociological and a more semiological/aesthetic approach. From this perspective, my concern will be in establishing the interdisciplinarity between Visual Culture and Cultural Studies and, in so doing, I will explore the relationship between the photograph, documentary practice, social processes, modes of representation and/or visual testimony, confirming Irit Rogoff's (1998) claim that "[I]mages do not stay within discrete disciplinary fields (…), since neither the eye nor the psyche operates along or recognizes such divisions. Instead they provide the opportunity for a mode of new cultural writing existing at the intersections of both objectivities and subjectivities".


Introduction: Shigella infections caused by gram-negative bacilli intestinal has created problems in the developed and developing countries. Indiscriminate use of antibiotics, regardless of the resistance has caused the emergence of resistant strains. The aim of this study was to investigate the prevalence of sulfonamide resistance genes and class 1 integron in Shigella sonnei strains isolated from patients with diarrhea and determination of antibiotic susceptibility of the isolates. Materials &methods: A total of 60 isolates were collected out of the Shigella Sonnei bacteria isolated from fecal infection at Kerman hospitals and cultured in specific media and then confirmed by biochemical tests. Sulfonamide resistance genes were studied including sulI and sulII and intI1 by Multiplex-PCR methods. Antibiotic susceptibility was determined to 8 isolates to different antibiotics by disk diffusion method. Findings: As a result, M-PCR was found in one-sample SulI genes and gene sulII genes in 32 samples, but intI1 gene was not detected in any of the strains. The results demonstrated the greatest resistance to antibiotic of Nalidixic acid (96.6%) and the highest sensitivity to ciprofloxacin(92.1%), respectively. Conclusion & discussion: Our study proved the resistance of Shigella sonnei strains to antibiotics. Therefore, it is essential to take deep medical care and conduct an appropriate use of antibiotics to prevent the spread of resistant strains. In addition, it was found that the gene sulII was the most frequent resistance gene to sulfonamide.


Factors Present at Enrollment of College Freshmen That Predict Placement in Developmental Courses at Select Private Institutions Attrition of college freshmen due, in part, to the lack of academic preparedness upon enrolling in college is an issue facing college and university administrators. Chief academic officers cannot ignore the fact that 30% of all students enrolling in postsecondary institutions require some form of "developmental" coursework. Institutional leaders need to be aware of predictors that determine the student's need for enrollment in developmental courses and factors that influence student persistence. Administrators must focus on both the characteristics and experiences of students prior to college, as well as their experiences inside the classroom, and how these variables interrelate. To understand the variables that predict enrollment in developmental courses and the role developmental courses play in persistence, alumni (n=1725) from six select postsecondary institutions were surveyed. This was a survey research design involving a self report questionnaire, the College Student Persistence Questionnaire (CSPQ). There were 414 (24%) completed questionnaires returned. The grouping variable (dependent variable) was enrollment in one or more developmental courses. The predictor variables (independent variables) were gender, race, year of enrollment, high school grade point average (GPA), age at enrollment, withdrawal from an institution, year of graduation, transfer to an institution, attainment of a bachelor's degree, transfer from an institution and age at graduation. Significant differences were found at the p < .01 level with regard to high school GPA as a predictor of placement in developmental education courses. This study provides sufficient support for identifying the academic needs of first year students. Since student success is determined by student persistence, it is crucial that postsecondary institutions allocate funding for programs that support academic success for students. Developmental education is an institutional responsibility and it must be an institutional priority.


It is well-known that overparametrized neural networks trained using gradient based methods quickly achieve small training error with appropriate hyperparameter settings. Recent papers have proved this statement theoretically for highly overparametrized networks under reasonable assumptions. These results either assume that the activation function is ReLU or they depend on the minimum eigenvalue of a certain Gram matrix. In the latter case, existing works only prove that this minimum eigenvalue is non-zero and do not provide quantitative bounds which require that this eigenvalue be large. Empirically, a number of alternative activation functions have been proposed which tend to perform better than ReLU at least in some settings but no clear understanding has emerged. This state of affairs underscores the importance of theoretically understanding the impact of activation functions on training. In the present paper, we provide theoretical results about the effect of activation function on the training of highly overparametrized 2-layer neural networks. A crucial property that governs the performance of an activation is whether or not it is smooth: • For non-smooth activations such as ReLU, SELU, ELU, which are not smooth because there is a point where either the first order or second order derivative is discontinuous, all eigenvalues of the associated Gram matrix are large under minimal assumptions on the data. • For smooth activations such as tanh, swish, polynomial, which have derivatives of all orders at all points, the situation is more complex: if the subspace spanned by the data has small dimension then the minimum eigenvalue of the Gram matrix can be small leading to slow training. But if the dimension is large and the data satisfies another mild condition, then the eigenvalues are large. If we allow deep networks, then the small data dimension is not a limitation provided that the depth is sufficient. We discuss a number of extensions and applications of these results.


In recent years there has been an increase in using Enterprise Resource Planning (ERP) systems in large companies and government corporations mainly in developed countries. While there is wide adoption of ERP systems in Western economies, developing countries lag far behind. However, due to recent economic growth, developing countries such as Kenya are increasingly becoming major targets of ERP vendors. There is an urgent need for under- standing ERP implementation issues in developing countries, as ERP systems are still in their early stages in these countries. They face additional challenges related to economic, cultural and basic infrastructure issues. This research investigates the organisational and national context within which ERP is adopted and used in Kenya, and how the context and ERP influence each other. In general, this research is based on the need to study organisations in their societal contexts and information systems in their organisational settings.
The research contributes to the controversial debate on the conflict between standardisation imposed by ERP systems and localisation of business practices. This study provides some key insights into the implementation and use of ERP systems in the public and the private sectors in Kenya. Case study findings suggest that the company sector plays an important role in ERP implementations in several key dimensions. ERP systems with in-built business practices express the tendency toward standardisation. In addition, the study investigates the challenges faced by organisations implementing ERP systems in Kenya and factors influencing ERP upgrade decisions. Findings of this research suggest that ERP implementation and upgrade is influenced by, but not necessarily bound by, existing contextual factors - national and organisational. Two models, namely, the Empirical ERP Implementation Model (EEIM) and the Upgrade Decision Model (UDM), are developed to represent ERP implementation and upgrade practices. The EEIM helps to identify why there will be particularly high variance in potential outcomes and further validates which organisational contexts and ERP implementation configurations create options during ERP implementation and usage. The UDM makes a novel contribution by showing how different forces interact to bring an aggregate of influences to a threshold level where an ERP system upgrade becomes necessary.
The findings of this study also aid the management of organisations that are implementing
ERP systems to gain a better understanding of the likely challenges they may face and to enable them to put in place appropriate measures to mitigate the risk of implementation
failures. This study also proposes an IT strategy framework which can be used by organisations planning to implement ERP to align their business and IT strategy. Finally, the study provides practical guidelines to practitioners on ERP implementation and upgrade based on the experience of the case study organisations and the ERP consultants interviewed.


Current theory on transitional consumption seems to rest on the premises that (1) consumption facilitates role transitions; (2) consumers know how to consume their way through these transitions; (3) consumers are motivated to approach new roles; and (4) consumption solves liminality. This perspective, however, offers an incomplete picture of consumption's role in the management of major life transitions. This article explores the ways in which ambivalence is woven through consumption experiences in times of liminality. It reviews prior research on consumption, role transitions, and ambivalence in the context of women's transition into motherhood. Findings are presented from an international interpretive study of women's consumption experiences during their transition to motherhood. This paper's findings suggest that while consumption can indeed play a positive role during role transitions, it can also, at other times, make transition a complicated, complex and confusing process.


The paper analyzes developments in TARGET2 imbalances within the euro area since 2007, from two perspectives: national central banksi?½ balance sheets and countriesi?½ balance of payments (BoP). We examine the relationship between TARGET2 balances and the Eurosystem liquidity provision, analyzing how the circulation of the latter has changed during the crisis. We then study BoP developments in Greece, Portugal, Italy and Spain, investigating which of the following explanations accounts for the growing TARGET2 imbalances: (i) current account deficit, (ii) decrease of net inflows of private capital from securities and interbank markets and (iii) run on deposits. The results of our analysis suggest that while the increase in TARGET2 liabilities is related to the current account deficit in Greece, there is no evidence of this in Italy, Spain and Portugal. In all countries the increase is mostly driven by private capital outflows in securities and interbank markets; deposit runs are apparent only in Greece. In Italy, the reduction of capital inflows consisted entirely in a decrease in the interbank market cross-border activity and in portfolio investments by non-residents.


The work presented
 in this thesis shows the study of different parameters of ion beam
 emanated from a conventional 2.3 kJ plasma focus device which are
 used for the deposition of thin films on zirconium substrate. These
 energetic ions are characterized by employing BPX65 photodiode
 detector placed at 9 cm along the anode axis and is used to estimate
 ion energy (range from 40 keV to 1.2 MeV) and ion number density
 (9.7×1019 m- 3 to 1.796×1019 m-3) of the ions emitted during one
 focus shot. The relativistic electrons emitted from DPF device play
 a vital role to incorporate the third element (ablated from the
 insert material placed at the anode tip by the bombardment of
 relativistic electrons) into the substrate matrix and to deposit
 composite films on different substrates.
 The composite films are characterized by employing different
 characterization techniques such as XRD, SEM, EDS, Raman
 Spectroscopy and Vickers microhardness tester to explore the diverse
 surface properties (crystal structural, surface morphology,
 crystallite size, microstructure features, elemental compositions
 and surface microhardness) of the composite films. TRIM code and
 micro-indentation measurements are used to estimate the depth
 profile of the modified layers.
 Nitriding of zirconium by employing the energetic nitrogen ions
 emanated from plasma focus device for multiple focus shots when the
 samples are placed at different angular positions confirms the
 formation of zirconium nitride films on zirconium substrate. The
 crystallinity and crystallite size of nitride phases increase with
 the increase of focus deposition shots while residual stresses are
 maximum at lower nitrogen content (lower number of focus shots)
 which decrease with the increase of nitrogen contents. Smooth and
 uniform surface morphology showing granular features of nitrides is
 observed at 10o. The nitrogen content in the deposited films
 increases with the increase of focus deposition shots. The
 microhardness of the deposited film enhances up to 400% and
 increased by increasing the nitrogen ion dose and decreases rapidly
 by increasing the angular position. Hence different features of the
 deposited films are strongly influenced by ion energy flux, ion
 number density and sample angular position.
 The XRD patterns of zirconium oxynitride nanocomposite film
 (deposited for 40 focus shots at different axial positions) show
 that the crystallinity of ZrN, Zr3N4 and ZrO2 depends on the sample
 axial position as well as ion energy flux. The SEM images show the
 formation of compact layer at lower axial position which is due to
 high ion energy flux. The nitrogen content decreases with the
 increase of sample angular position. The maximum microhardness of
 the layers is found to be 7200 ± 12 MPa for 10 gram imposed load.
 The EDS exhibits the distribution of different elements present in
 the composite films.
 ZrAlON composite films are deposited on zirconium substrate showing
 the formation of ZrN, Al2O3 and AlN compounds. Five focus shots are
 sufficient to initiate the nucleation of ZrN and Al2O3 while 10
 focus shots are enough to initiate the nucleation of AlN. The
 crystal growth of nitrides/oxides increases with increasing focus
 shots (up to 30 focus shots) and after that re-sputtering of the
 previously deposited film takes place. Smooth surface is observed
 for 20 focus shots at 0o angular position while net type
 microstructure is obtained for 30 focus shots. Rough surface
 morphology is observed for 40 focus shots. A typical microhardness
 value of the deposited composite films is 5255 ± 10 MPa for 10 grams
 imposed load which is 3.3 times the microhardness values of
 unexposed sample. The microhardness values of the exposed samples
 increase with increasing focus shots (up to 30 Focus shots) and
 decrease for 40 focus shots due to re-sputtering of the previously
 deposited composite film.
 Nanocrystalline zirconium carbonitride (ZrxCNy) composite films
 composed of ZrN, Zr2N and Zr3N4, ZrC and Zr2CN ompounds are
 deposited on zirconium substrate at room temperature for multiple
 focus shots. The average crystallite sizes estimated for ZrN (200)
 and Zr2CN (111) planes are found to vary from 10 to 20 nm. Maximum
 compressive stresses (~ 3.9 GPa) in Zr2N (002) plane for 30 focus
 shots while maximum tensile stresses (~ 6.5 GPa) in ZrN (200) plane
 for 20 focus shots are observed. Tensile stresses in Zr2CN (111)
 plane are transformed to compressive one after 30 focus ion
 irradiation. Raman analysis exhibits the emergence of D and G bands
 relating to carbides phases during the deposition process. The SEM
 microstructure shows agglomerates of size 30 to 300 nm. The Vickers
 microhardness values of the composite films increase with the
 increase of focus shots and is found to be 5.6 ± 0.45 GPa for 10 g
 imposed load which is 4.5 times that of the untreated substrate and
 1.5 ± 0.11 GPa for 200 g imposed load which is 1.3 times that of the
 virgin one.
 Zirconium silicon nitride composite films consisting of Si3N4 and
 Zr3N4 compounds are deposited on silicon substrate at room
 temperature through the reaction of sputtered silicon by ion beams
 and ablated zirconium from the insert by using plasma focus device.
 The crystallinity of Si3N4 and Zr3N4 compounds increases with
 increasing ion irradiation. The crystallite size of nitride
 increases (from 9 ± 1 nm to 33 ± 3.5 nm) while % microstrain values
 developed in the nanocomposite films decrease (from 3.65 to 0.61)
 with increasing focus shots. The SEM images reveal different
 microstructure patterns like granular, oval and cauliflower types of
 the deposited films. It is found that crystal growth and stress
 relaxation inhibit the pit formations during the deposition process.
 The EDS results confirm the presence of silicon, zirconium, nitrogen
 and oxygen in the composite films.


This dissertation looks at Romanian ethnomusicology, primarily through analyzing the publications of one important research institution, the Institut de Etnografie și Folclor and its predecessors. It covers a period from the 19th century to the 1970s. This study utilizes the archaeological approach (derived from M. Foucault's book The Archaeology of Knowledge) to map the ethnomusicological knowledge produced at the Institute and investigates uses of this knowledge, primarily in the field of cultural politics. The study begins chronologically in the 19th century when folk music first became a topic in an emerging field that today is known as folkloristics. The study shows the importance of academic folklore research in relation to the political project of Romanian independence. In the 1920s, in large part due to the activities of Constantin Brăiloiu, a new subdiscipline emerged that became known as folclor muzical (musical folklore). This new discipline was based on a new, more formal and more technical notion of music as pioneered in Romanian discourse by Bela Bartok and others. Brăiloiu (and his adversary G. Breazul) founded folk music archives in the late 1920s that were later transformed into the Institute de Etnografie și Folclor. With the takeover of the communists, the Institute was integrated into the Stalinist cultural policy. Institute in Bucharest played an important role in context, overseeing the work of other folklorists and ethnomusicologists in the country. It is likely that the Institute was supposed to check if other folklorists in the country complied with political demands. After 1956 and in particular under the director Mihai Pop in the early years of Ceausescu's rule (around 1965), the ethnomusicologists at the Institute find a modus vivendi that allows them to engage in productive research with a noticeable amount of autonomy. However, since the implementation of the Stalinist regime of cultural policy in the late 1940s, the public image of folk music was largely governed by communist images and researchers, ethnomusicologists among them, were typically only visible in the public when they confirmed the official political line. Around 1970 a new phase began both in Romanian politics at large, with Ceausescu's travelling to China and North Korea, and in the Institute. Under new directorship and after several reorganizations, the ethnomusicologists lost influence mostly to so-called literary folklorists. At the same time, a new research agenda encouraged them to concentrate on musical typologies that -- in contrast to their own proclamations -- lead the Institute's ethnomusicologists to work that was more removed from the principles established by Constantin Brăiloiu.


This study aims to analyze the effect of piston bowl geometry on the combustion and emission performance of the syngas-fueled homogenous charge compression ignition (HCCI) engine, which operates under lean air–fuel mixture conditions for power plant usage. Three different piston bowl geometries were used with a reduction of piston bowl depth and squish area ratio of the baseline piston bowl with the same compression ratio of 17.1. Additionally, exhaust gas recirculation (EGR) is used to control the maximum pressure rise rate (MPRR) of syngas-fueled HCCI engines. To simulate the combustion process at medium load (5 bar indicated mean effective pressure (IMEP)) and high loads of (8 and 10 bar IMEP), ansys forte cfd package was used, and the calculated results were compared with Aceves et al.'s Multi-zone HCCI model, using the same chemical kinetics set (Gri-Mech 3.0). All calculations were accomplished at maximum brake torque (MBT) conditions, by sweeping the air–fuel mixture temperature at the inlet valve close (TIVC). This study reveals that the TIVC of the air–fuel mixture and the heat loss rate through the wall are the main factors that influence combustion phasing by changing the piston bowl geometry. It also finds that although pistons B and C give high thermal efficiency, they cannot be used for the combustion process, due to the very high MPRR and NOx emissions. Even though the baseline piston shows high MPRR (23 bar/degree), it is reduced, and reveals an acceptable range of 10–12 bar/degree, using 30% EGR.


The Lower Cretaceous Captain Sandstone Member of the Inner Moray Firth has significant potential for the injection and storage of anthropogenic CO2 in saline aquifer parts of the formation. Pre-existing faults constitute a potential risk to storage security owing to the elevated pore pressures likely to result from large-scale fluid injection. Determination of the regional in situ stresses permits mapping of the stress tensor affecting these faults. Either normal or strike-slip faulting conditions are suggested to be prevalent, with the maximum horizontal stress orientated 33°–213°. Slip-tendency analysis indicates that some fault segments are close to being critically stressed under strike-slip stress conditions, with small pore-pressure perturbations of approximately 1.5 MPa potentially causing reactivation of those faults. Greater pore-pressure increases of approximately 5 MPa would be required to reactivate optimally orientated faults under normal faulting or transitional normal/strike-slip faulting conditions at average reservoir depths. The results provide a useful indication of the fault geometries most susceptible to reactivation under current stress conditions. To account for uncertainty in principal stress magnitudes, high differential stresses have been assumed, providing conservative fault-stability estimates. Detailed geological models and data pertaining to pore pressure, rock mechanics and stress will be required to more accurately investigate fault stability.


Informal international regulatory cooperation is changing into recognizable forms of international administration. This paper surveys some of those forms. The forms range from hard procedural law to soft harmonization-through-example. They include: 1) hard international rules that constrain institutions in developed countries; 2) softer principles of supervision which bureaucrats in developing countries may emulate; and 3) models for regulators in adjacent issue areas. It is in attempting to adopt hard rules that we see an escalating procedural formality to regulatory cooperation. We also see a softer proselytization of unobjectionable, easy (for already sophisticated regulators, at least) standards throughout the developing world. Finally, the horde of organizations that have copied the form and agendas of established regulatory cooperation mechanisms also play a part in emerging international administration. The principal case studies for the paper come from international financial regulation.


Extracted from text ... W
18 Management Today April 2006
Dr Ren Pellissier is professor of information
management and dean of the faculty
of business management at CIDA City
Campus. She is the founding member of
Ymholiad International Institute for
Leadership and Innovation and has
published extensively in the areas of
information, leadership and complexity
science including her book, Searching for
the Quantum Organisation: The IT Circle
of Excellence.
This is the second in a four part series
on technology and innovation.
Information (r)evolution:
leadership in information or
information in leadership?
What is wrong with modern organisations?
There are generally one of two ..


Introduction: Dipyridamole is an Anti-platelet agent exhibits release problems at higher pH of small intestine due to its pH dependent solubility and precipitation followed by interruption of drug release from dosage form. To overcome this extended release formulation was developed by using pH modulating agent (tartaric acid). Objective: Present study was undertaken with a view of the formulations evaluated by performing dissolution testing on developed extended released tablets. Method: development of dissolution method at different time points and USP Apparatus 1 (basket) and 2 (paddle) at rotating speeds of 50 or 100 rpm used to evaluate the release characteristics of the formulations. Furthermore, solubility and in vitro dissolution studies of formulated tablets were performed at pH values of 1.2 and 5.5. Results: In this study we found increasing volume of dissolution medium pH 5.5 phosphate buffers drug precipitation is increased. The developed dissolution method was validated according to ICH guidelines for various parameters such as specificity, accuracy, precision, and stability. The dissolution method was confirmed by determining the dissolution rate of extended released Dipyridamole tablets containing pH modulating agent. The best in vitro dissolution profile was obtained using pH 5.5 phosphate buffer as the dissolution medium (500 ml) stirred at 100 rpm. A comparison of the dissolution profiles in official and developed media showed significant differences based on f1 and f2 values. Conclusion: The developed dissolution test exhibited a higher capacity than the compendia methods in differentiating the release profiles of pH independent extended release tablets. It can be applied during formulation development and quality control analysis of pH independent extended release tablets for evaluation of the effects of pH modifier in dissolution medium and processing parameters.


Self-ignited, naturally occurring coal fires and fires resulting from human activities persist for decades in underground coal mines, coal waste piles, and unmined coal beds. These uncontrolled coal fires occur in all coal-bearing parts of the world (Stracher, 2007) and pose multiple threats to the global environment because they emit greenhouse gases—carbon dioxide (CO2), and methane (CH4)—as well as mercury (Hg), carbon monoxide (CO), and other toxic substances (fig. 1). The contribution of coal fires to the global pool of atmospheric CO2 is little known but potentially significant. For China, the world's largest coal producer, it is estimated that anywhere between 10 million and 200 million metric tons (Mt) of coal reserves (about 0.5 to 10 percent of production) is consumed annually by coal fires or made inaccessible owing to fires that hinder mining operations (Rosema and others, 1999; Voigt and others, 2004). At this proportion of production, coal amounts lost to coal fires worldwide would be two to three times that for China. Assuming this coal has mercury concentrations similar to those in U.S. coals, a preliminary estimate of annual Hg emissions from coal fires worldwide is comparable in magnitude to the 48 tons of annual Hg emissions from all U.S. coal-fired power-generating stations combined (U.S. Environmental Protection Agency, 2002). In the United States, the combined cost of coal-fire remediation projects, completed, budgeted, or projected by the U.S. Department of the Interior's Office of Surface Mining Reclamation and Enforcement (OSM), exceeds $1 billion, with about 90% of that in two States—Pennsylvania and West Virginia (Office of Surface Mining Enforcement and Reclamation, 2008; fig. 2). Altogether, 15 States have combined cumulative OSM coal-fire project costs exceeding $1 million, with the greatest overall expense occurring in States where underground coal fires are predominant over surface fires, reflecting the greater cost of extinguishing underground fires (fig. 2) (see "Controlling Coal Fires"). In this fact sheet we review how coal fires occur, how they can be detected by airborne and remote surveys, and, most importantly, the impact coal-fire emissions may have on the environment and human health. In addition, we describe recent efforts by the U.S. Geological Survey (USGS) and collaborators to measure emissions of CO2, CO, CH4, and Hg, using groundbased portable detectors, and combining these approaches with airborne thermal imaging and CO2 measurements. The goal of this research is to develop approaches that can be extrapolated to large fires and to extrapolate results for individual fires in order to estimate the contribution of coal fires as a category of global emissions.


Entrepreneurship is said to be the answer for job creation, but little explanation is offered on how to perform entrepreneurship. This thesis aims to reduce the gap by exploring how a high growth venture can be built. In this paper the entrepreneurial process was explored through a comparative case study, examining five entrepreneurs who have repeatedly built successful ventures. First and foremost, this paper found that it is possible to create a model giving practical advice on how to build a high growth venture. The paper found that the goal of the model was to find a product market fit, meaning that the product being sold was bought. But fit was found to exist in various degrees. For high growth ventures two factors of fit were commonly found optimized. They had one, a repeatable and scalable business model which delivered high value for customers. And two, a definition of the tiniest possible product which could be sold. In total these two factors were found to maximize margins which gave profit to fuel growth. The model for building a high growth venture was found to optimize the fit in an iterative process revolving around the customer. When a sufficient fit was found the venture changed from performing exploration to exploitation of the fit, which meant high growth given a good enough fit.


This paper investigates a long-run relation for the trade weighted NOK exchange rate. I find that the NOK Trade Weighted Index (TWI) cointegrates with the real oil price, the price differential and the real interest differential. The paper documents a long-run solution for the TWI. The paper's main contribution is that the analysis is based on a test for cointegration that is robust to mixed orders of integration in the data. The estimated long-run relation can be considered a benchmark for the nominal exchange rate. This interpretation allows the model to be used when analysing deviations of the nominal exchange rate from the model consistent level. The model is part of the suit of simple cross check models used when analysing the exchange rate in Norges Bank. I also find that the long-run relation is robust to the recent problems in the financial markets.


This paper presents a post-rehabilitation monitoring and modeling study of the sanitary sewer system at Lawrence Livermore National Laboratory (LLNL). The study evaluated effectiveness of sewer system rehabilitation efforts and defined benchmarks for environmental success. A PCSWMM model for the sanitary sewer system was developed and applied to demonstrate the success of a $5 million rehabilitation effort. It determined that rainfall-dependent inflow and infiltration (RDI&I) had been reduced by 88%, and that system upgrades adequately manage predicted peak flows. An ongoing modeling and analysis program currently assists management in evaluating the system`s needs for continuing maintenance and further upgrades. This paper also summarizes a 1989 study that evaluated data collected from December 1, 1988, to January 6, 1989, to determine the adequacy of the LLNL sewer system to accommodate present and future peak flows, and the Sanitary Sewer Rehabilitation (SSR) project, which took place from 1991 through 1995.


Throughout history, religion, spirituality, health, and the practice of medicine have been intertwined but are all united in seeking inproved health for all. Medical organizations and faith-based institutions consider caring for the sick as their primary mission, sometimes drawing from each other's knowledge about healing to address patients' concerns. This paper examines the role of spirituality and religion on the health of a populace and explains how a faith-based organization uses spirituality as the foundation for communicating health even as the community avails itself of medical science through the provision of a barangay health center.


Since the introduction of African swine fever virus (ASFV) into the Baltic states and Poland in 2014, the disease has continued to spread within these regions. In 2017, the virus spread further west and the first cases of disease were reported in the Czech Republic and Romania, in wild boar and domestic pigs, respectively. To control further spread, knowledge of different modes of transmission, including indirect transmission via a contaminated environment, is crucial. Up until now, such an indirect mode of transmission has not been demonstrated. In this study, transmission via an environment contaminated with excretions from ASFV-infected pigs was investigated. Following euthanasia of pigs that were infected with an isolate of ASFV from Poland (POL/2015/Podlaskie/Lindholm), healthy pigs were introduced into the pens, in which the ASFV-infected pigs had been housed. Introduction was performed at 1, 3, 5 or 7 days, following euthanasia of the infected pig groups. Pigs, that were introduced into the contaminated environment after 1 day, developed clinical disease within 1 week, and both ASFV DNA and infectious virus were isolated from their blood. However, pigs introduced into the contaminated pens after 3, 5 or 7 days did not develop any signs of ASFV infection and no viral DNA was detected in blood samples obtained from these pigs within the following 3 weeks. Thus, it was shown that exposure of pigs to an environment contaminated with ASFV can result in infection. However, the time window for transmissibility of ASFV seems very limited, and, within our experimental system, there appears to be a rapid decrease in the infectivity of ASFV in the environment.


INTRODUCTION The mites of the genus Hyadesia are of cosmopolitan distribution. They live in the intertidal area where they feed mainly on algae in salt water. Up to now 16 species have been described in this genus. Most of these species have been inadequately described and it is generally very difficult to recognize them from the original description and figures. Through the courtesy of Dr. L. van der Hammen of the Leiden Museum, we were able to examine the hyadesid mites conserved in that Museum. The present paper is devoted to the study of this collection. It allows us to redescribe Hyadesia vietsi Womersley, 1961, and to record some new localities for Hyadesia fusca (Lohmann, 1894). Hyadesia vietsi Womersley, 1961 (figs. 1-7) This species is known after two female specimens. The holotype is in the Rijksmuseum van Natuurlijke Historie at Leiden, the paratype in the South Australian Museum. Redescription of the female holotype (figs. 1-7). — Length of idiosoma 560 μ, maximum width 375 μ. Dorsum: Propodosomal shield wider than long. The cuticle behind this shield is soft. There is a small depression behind the sc i and sc e setae, representing a vestigial sejugal furrow. Oil glands very large. From the orifice of the oil-gland arise, at each side, two narrow and shallow furrows, one directed anteriad, the other posteriad. These two furrows present several branches, some of them ending into oval symmetrical orifices. A similar structure of oil furrows has already been described in other species of Hyadesia (Fain, 1975). Venter: Genital suckers not observed. Anus termino-ventral.


Collision avoidance plays a crucial role in safe multirotor flight in cluttered environments. Even though a given reference trajectory is designed to be collision free, it might lead to collision due to imperfect tracking caused by external disturbances. In this work, we tackle this problem by computing the forward reachable set (FRS), which is the set of positions and velocities that a multirotor can reach while following a reference trajectory due to tracking errors. Hence, if the FRS is computed before flight, we can utilize it to check the safety of a given trajectory in terms of collision avoidance. To compute a realistic FRS that covers an agile flight envelope, we consider first-order aerodynamic effects, which have the most salient influence on the vehicle. For computing FRS, we conduct a thorough stability analysis including these aerodynamic effects. Then, we present an FRS computation method that can easily be adapted to newly given reference trajectories. The presented method is validated by comparing the FRS with real flight data collected during agile and high-speed flight. In addition, we compare the FRS computed with and without compensating for first-order aerodynamic effect to highlight their significance on the trajectory tracking performance. To the best of our knowledge, this is the first attempt to compute FRSs by incorporating first-order aerodynamic effects for multirotors.


The primary function of plasma lipoproteins is to transport newly synthesised or dietary lipids in the circulation; these water-insoluble substances include triacylglycerol, cholesterol and fat-soluble vitamins. Mutations in genes for the many enzymes, receptors and structural proteins that regulate lipoprotein metabolism and transport are often detrimental to health, and may increase the amount of normal lipoproteins, result in accumulation of abnormal lipoproteins or cause lipoprotein deficiencies. Some defects increase the risk of coronary heart disease, whereas other deficiency disorders cause neurological and/or gastrointestinal symptoms. Genetic disorders of lipoprotein metabolism highlight the importance of lipid transport and metabolism in normal human physiology.

Key Concepts

Normal regulation of plasma lipoprotein metabolism is critical for transport of lipids and fat-soluble vitamins in the circulation.

Once secreted from cells in the liver or intestine, lipoproteins undergo many complex metabolic changes in the blood circulation brought about by enzymes and their cofactors, exchange factors and cell-surface receptors.

Variation in the genes for these proteins can alter their function and cause changes in the composition, concentration and/or function of plasma lipoproteins that are frequently deleterious to health.

Several defects in lipoprotein metabolism result in increased risk of premature coronary heart disease because of cholesterol deposition in the blood vessels, whereas others lead to neurological symptoms due to deficiency of fat-soluble vitamins.

The inheritance pattern varies: most known lipoprotein disorders are monogenic, with either autosomal dominant inheritance, where heterozygous carriers are affected or autosomal recessive inheritance, where heterozygous carriers are apparently unaffected. Some dominantly inherited disorders have a gene dosage effect, where homozygous individuals are more severely affected than heterozygous ones.

Some gene variants only have a marked physiological effect in a particular genetic or environmental background, so not all carriers are affected.

Families exist who have a clinical phenotype characteristic of a known monogenic disorder, but who have no detectable defect in the known causal genes; this suggests that novel genes still remain to be identified that influence lipoprotein metabolism.

One of the commonest inherited disorders, familial combined hyperlipidaemia, is not monogenic and requires several gene variants to be present for symptoms to be manifest. These variants are also unlikely to be the same for all families.

Keywords:

lipid metabolism;
atherosclerosis;
hyperlipidaemia;
coronary heart disease;
mutations;
fat-soluble vitamin deficiency


Patients with familial isolated pituitary adenoma are predisposed to pituitary adenomas, which in a subset of cases is due to germline inactivating mutations of the aryl hydrocarbon receptor–interacting protein (AIP) gene. Using Cre/lox and Flp/Frt technology, a conditional mouse model was generated to examine the loss of the mouse homolog, Aip, in pituitary somatotrophs. By 40 weeks of age, >80% of somatotroph specific Aip knockout mice develop growth hormone (GH) secreting adenomas. The formation of adenomas results in physiologic effects recapitulating the human syndrome of acromegaly, including increased body size, elevated serum GH and insulin-like growth factor 1 levels, and glucose intolerance. The pretumorigenic Aip-deficient somatotrophs secrete excess GH and exhibit pathologic hyperplasia associated with cytosolic compartmentalization of the cyclin-dependent kinase (CDK) inhibitor p27kip1 and perinuclear accentuation of CDK-4. Following tumor formation, the Aip-deficient somatotrophs display reduced expression of somatostatin receptor subtype 5 with impaired response to octreotide. The delayed tumor emergence, even with loss of both copies of Aip, implies that additional somatic events are required for adenoma formation. These findings suggest that pituitary hyperplasia precedes adenomatous transformation in somatotroph-specific Aip-deficient mice and reveal potential mechanisms involved in the pretumorigenic state that ultimately contribute to transformation.


This paper concerns the application of fuzzy clustering methods in the evaluation of compost bedded pack (CBP) barns. Fuzzy classifiers are developed to assist decision making regarding the control of variables such as bed moisture, temperature and bed aeration. The idea is to identify interactive factors and therefore promote dairy cattle welfare and improve productivity indices. The data was obtained from 42 CBP barns in the state of Kentucky, US. Details about the data acquisition methodology are given. Well-known clustering methods, namely K-Means (KM), Fuzzy C-Means (FCM), Gustafson-Kessel (GK), and Gath-Geva (GG), are considered for data analysis. The efficiency of the methods is determined by validation indices such as the Xie-Beni criterion, Partition Coefficient, and Partition and Dunn indices. Six classes related to the degree of efficiency of the composting process were identified. The GG method showed to be the most accurate according to the majority of the validation indices, followed by GK. The main reason for the best results is the use of maximum-likelihood-based and Mahalanobis distance measures. Fuzzy modeling results and linguistic information have shown to be useful to help decision making in farms that adopt CBP barns as containment systems for dairy cattle.


Acute rheumatic fever (ARF) is still a major health problem in South Africa. In this retrospective, descriptive study, 100 patients with ARF were analysed to establish whether the clinical profile has changed. Carditis was found in 94% of patients and was therefore the most common of the major criteria found at presentation. The two most common early complications were congestive cardiac failure (CCF) in 16% and infective endocarditis (IE) in 5% of patients. Late complications were CCF in 35% with IE contributing to CCF in 10% of patients. A further 15% developed IE. In conclusion, the profile of ARF as described in the literature has changed, with carditis now being the most common manifestation.


A hydrostatic test is a way in which pressure vessels such as pipelines, plumbing, gas cylinders, boilers and fuel tanks can be tested for strength and leaks. The test involves filling the vessel or pipe system with a liquid, usually water, which may be dyed to aid in visual leak detection, and pressurization of the vessel to the specified test pressure. Pressure tightness can be tested by shutting off the supply valve and observing whether there is a pressure loss. The location of a leak can be visually identified more easily if the water contains a colorant. Strength is usually tested by measuring permanent deformation of the container. Hydrostatic testing is the most common method employed for testing pipes and pressure vessels. Using this test helps maintain safety standards and durability of a vessel over time. Newly manufactured pieces are initially qualified using the hydrostatic test. They are then re-qualified at regular intervals using the proof pressure test which is also called the modified hydrostatic test .Testing of pressure vessels for transport and storage of gases is very important because such containers can explode if they fail under pressure. Hydrostatic tests are conducted under the constraints of either the industry's or the customer's specifications, or may be required by law. The vessel is filled with a nearly incompressible liquid - usually water or oil - pressurized to test pressure, and examined for leaks or permanent changes in shape. The test pressure is always considerably higher than the operating pressure to give a factor of safety.


The objective of this thesis is to identify and recommend leadership styles and strategies for Kingsway Hospital within the Netcare Group corporate culture to re-dress the unacceptable leadership style currently in operation, a declining business life cycle and a potential threat to financial sustainability. The thesis commences with an in depth discussion of the various leadership theories in context; starting from the rudimentary and culminating in the sophisticated Hersey and Blanchard Situational Behavior theories. Interestingly, the basic leadership dimensions have been retained throughout the years by the different theorists, with each subsequent theorist expanding on the original leadership qualities. This chapter concludes with the author's composite model ofleadership, resulting in effective leadership, underpinned by corporate culture. The case study situation is described in detail, using the same criteria as the author's composite model of leadership. The core issue is the current Hospital General Manager's leadership, his behavior and action within the work environment. Two organizational strategies were identified in the case study; albeit they were not being currently implemented. Evaluation of the theory and case study led to the conclusion that are gaps between the current incumbent's skills and the composite model ofleadership , posing a potential internal as well as external threat and lost opportunities for Kingsway Hospital. The internal threat is of a human nature; high staff turnover and the external threat could result in potential lost opportunities, patients and competitor threat. The two strategies identified will be presented as the core strategies relevant to Kingsway Hospital. Finally, the recommendations will be given after having completed an in depth evaluation of the case study, identification of the core strategies and assessing the benefits. Most of the recommendations are for immediate implementation, while some span over short to medium term. The recommendations are geared towards retaining the current Hospital General Manager, but with a changed leadership style. However, if there is no change in the status quo, the worst case scenario will be to transfer the Hospital General Manager to a position that does not involve a high degree of people interaction, as is the current situation. Clearly, from this case study, the recommendations contained in this thesis are to be implemented as a matter of urgency to ensure stability, sustainability, continuity and finding a resolution to the problem statement. If staff is the assets of the Netcare Group, then immediate action is necessary to protect them.


Nearly every American woman will, at some point during her working life, be sexually harassed, according to Raymond F. Gregory, a lawyer specializing in employment and discrimination law. This book provides information for those victims as well as for those suffering same sex harassment and for male victims of sexual harassment. Gregory analyzes sexual harassment from the perspective of existing federal law and describes the legal rights that may be asserted by victims of harassment to obtain either injunctive or monetary relief. By clarifying little understood aspects of the law barring sexual harassment, the author presents an indispensable resource for victims seeking to learn what to expect from the legal system if they contest the actions of their harassers in the courts.


Dehydroabietic acid (DHAA) is a naturally occurring component of pine resin that was recently shown to open voltage-gated potassium (KV) channels. The hydrophobic part of DHAA anchors the compound near the channel's positively charged voltage sensor in a pocket between the channel and the lipid membrane. The negatively charged carboxyl group exerts an electrostatic effect on the channel's voltage sensor, leading to the channel opening. In this study, we show that the channel-opening effect increases as the length of the carboxyl-group stalk is extended until a critical length of three atoms is reached. Longer stalks render the compounds noneffective. This critical distance is consistent with a simple electrostatic model in which the charge location depends on the stalk length. By combining an effective anchor with the optimal stalk length, we create a compound that opens the human KV7.2/7.3 (M type) potassium channel at a concentration of 1 µM. These results suggest that a stalk between the anchor and the effector group is a powerful way of increasing the potency of a channel-opening drug.


Voltage-gated calcium (Cav) channels are essential components of excitable cells.
The function of neurons is highly dependent on the plasma membrane availability of
Cav channels, which allow entry of Ca2+. Cav channels control a variety of processes,
including synaptic transmission and muscle contraction.
Alpha-2-delta (α2δ), an auxiliary subunit of Cav channels increases the current
amplitude of by about 4-fold through supporting membrane trafficking of the ionconducting
Cav alpha-1 subunit. Furthermore, α2δ modulates the biophysical channel
properties. The α2δ-1 isoform has an important pharmacological role of binding
antiepileptic gabapentinoid drugs. Additionally, α2δ regulation is enhanced in
neuropathic pain models.
Until recently, α2δ was characterized as a Type I transmembrane protein. We have
identified that α2δ is instead anchored to the extracellular leaflet of the plasma
membrane via a glycosyl-phosphatidylinositol (GPI) anchor. This type of membrane
attachment plays an important role in sorting proteins to specialized domains of the
lipid bilayer, termed lipid rafts, allowing lateral movement, interactions and signal
transduction.
The first part of this thesis examines the regulatory properties of neuron-specific
α2δ-3 in association with the N-type Cav channel. The results obtained strongly support
the hypothesis that α2δ-3 is attached to the membrane via a GPI-anchor. This was
demonstrated by enzymatic PI-PLC cleavage, along with proteoglycan NotumWT
hydrolytic activity, both of which resulted in a significant reduction in the Ba2+ current.
These findings are further corroborated through the use of recombinant constructs of
α2δ-3, mutated at the GPI-attachment site. Together with immunofluorescence results,
which demonstrate reduced cellular transport of the two α2δ-3 constructs, it was
concluded that less channels reach the plasma membrane in the absence of an intact
GPI-signal sequence. Moreover, effects of acute and chronic cholesterol modulation on
Cav channels plasma membrane targeting were examined. In both instances, N-type
Cav/α2δ-3 function and distribution were impaired, providing additional support for the
importance of Cav channel localization to lipid raft regions.
The second part of this thesis examines the prediction that the α2δ-1 isoform is GPIanchored.
A C-terminal truncated form of α2δ-1 (DGPI α2δ-1) shows altered subcellular
and surface localization, as well as functional P/Q-type Cav/α2δ-1 channel
reduction, providing independent evidence that the GPI anchor of α2δ-1 facilitates Cav
channel functional expression. In the final section of the thesis, the WT and DGPI α2δ-1 were used to assess
cellular prion protein (PrPC) modulation on P/Q-type Cav/α2δ-1 trafficking using
electrophysiological and immunocytochemical methods. An interaction between the
WT α2δ-1 and PrPC was proposed, based on the findings that co-expression of the two
proteins resulted in a strong colocalization as well as altered channel function. The
implications of these results are highlighted by established findings that cellular PrP is
required for susceptibility to prion infections and for prion toxicity, and that mice
expressing anchorless PrP show reduced infectivity with the pathogenic scrapie PrP
isoform.


OBJECTIVE The aim of this study was to elucidate whether subclinical nerve dysfunction as reflected by neurophysiological testing predicts the development of clinical neuropathy in patients with type 1 diabetes. RESEARCH DESIGN AND METHODS Fifty-nine patients were studied twice with neurophysiological measurements at baseline and at follow-up. At baseline, patients were 15.5 ± 3.22 years (range 7–22 years) of age, and duration of diabetes was 6.8 ± 3.3 years. At follow-up, patients were 20–35 years of age, and disease duration was 20 ± 5.3 years (range 10–31 years). RESULTS At baseline, patients showed modestly reduced nerve conduction velocities and amplitudes compared with healthy subjects, but all were free of clinical neuropathy. At follow-up, clinical neuropathy was present in nine (15%) patients. These patients had a more pronounced reduction in peroneal motor nerve conduction velocity (MCV), median MCV, and sural sensory nerve action potential at baseline (P < 0.010–0.003). In simple logistic regression analyses, the predictor with the strongest association with clinical neuropathy was baseline HbA1c (R2 = 48%, odds ratio 7.9, P < 0.002) followed by peroneal MCV at baseline (R2 = 38%, odds ratio 0.6, P < 0.006). With the use of a stepwise forward analysis that included all predictors, first baseline HbA1c and then only peroneal MCV at baseline entered significantly (R2 = 61%). Neuropathy impairment assessment showed a stronger correlation with baseline HbA1c (ρ = 0.40, P < 0.002) than with follow-up HbA1c (ρ = 0.034, P < 0.007). CONCLUSIONS Early defects in nerve conduction velocity predict the development of diabetic neuropathy. However, the strongest predictor was HbA1c during the first years of the disease.


Surgery for early onset scoliosis (EOS) often requires instrumentation which enables the
pediatric patient's spine to grow. The drawback of growing rods (Ellipse Technologies, USA)
is the requirement of periodical extension (at least twice a year). In contrast, in growth-
guidance sliding devices such as the Shilla (Medtronic, USA) or LSZ-4D (Conmet, Russia)
the extension procedure is not necessary since only one or few fixtures are locked whilst other
fixtures make it possible for rods to slide allowing growth of the spine. However, due to the
absence of fusion in sliding devices increased rate of fractures of rods is possible.
Additionally, movement of rods against fixtures may result in the generation of wear debris.
Among traditional metallic materials used for such instrumentation titanium alloys are the
most biocompatible and are widely used as fixtures material, while Nitinol, an alloy with
Shape memory effect, is a promising material for rods due to having potential for more
gradual and sustained correction associated with its shape memory effect and potentially
reducing adjacent segment degeneration due to its super-elastic properties.
The aim of this thesis was to investigate complications associated with implantation of
growth-guidance sliding LSZ-4D in pediatric patients and to investigate the use of Nitinol and
titanium alloy (Ti6Al4V) for this application.
Analysis of retrieved components of LSZ growth-guidance sliding device (LSZ-4D) made
from titanium alloy (Ti6Al4V) implanted in paediatric patients together with associated
tissues showed metallosis which in some cases led to the development of complications
including seromas and fistula formation. These complications occurred in 5 out of the 25
patients investigated. Another 4 patients encountered fatigue fracture of rods.The volume
wear rate measured for the retrieved components of LSZ-4D was found to be 12.5 mm3 per
year. In these 25 patients with implanted LSZ-4D devices there was a statistically significant
increase in titanium and vanadium ions in the whole blood.
With a view to replacing titanium alloy rods with Nitinol an investigation on the fatigue
behaviour of Nitinol revealed that creating a microstructure which increased deformation due
to a martensitic phase transformation improved high strain amplitude fatigue resistance of
Nitinol, whereas precipitation of nanosize Ni-rich particles and decreasing of Ti4Ni2ox
inclusions resulted in an increase in low strain fatigue resistance.
The wear behaviour of Nitinol in comparison to titanium alloy was also investigated and
showed that the wear resistance of Nitinol tested against titanium alloy (Ti6Al4V) in the simulated body environment is approximately 100 fold greater compared to titanium alloy
(Ti6Al4V) and is similar to that of CoCr alloy. Nevertheless, Nitinol - Ti6Al4V combination
still generates high volumetric wear associated with debris release from the Ti6Al4V
component.
Coating and treating the surface with TiN (titanium nitride), DLC (diamond like carbon)
coatings and ion implantation of nitrogen ions in some instances reduced the wear. The
deposition of a TiN coating only on the titanium component in a Nitinol - Ti6Al4V
combination significantly improved the wear performance and this was associated with the
protection of titanium component whereas the application of DLC improved the wear
performance of both titanium and Nitinol. [on implantation or deposition of TiN or DLC
coatings on both counterparts was found to be less effective.
The current study indicates the importance and potential of reducing the reliance on titanium
alloy by using Nitinol for patients with scoliosis and especially in those cases where relative
moment of the fixtures is required, such as in growing patients.


Unlike animals that have extensive families of G protein subunit genes, plants, such as Arabidopsis, appear to have a much more limited repertoire of G protein subunits. Arabidopsis has a single Gα gene (GPA1), a single Gβ gene, and two Gγ genes. Despite this lack of diversity, GPA1 mutants show several phenotypes consistent with a role in regulating cell division, stomatal aperture regulation, and responsiveness to several plant hormones, as well as sugars. These findings suggest that G proteins participate in several plant signaling pathways. In a yeast two-hybrid screen, Lapik and Kaufman identified Arabidopsis pirin (AtPirin1), which in mammals interacts with a CCAAT box-binding transcription factor, as a partner for GPA1. The promoter of Atpirin1 contained cis elements predicted to confer light and abscisic acid (ABA) regulation to the gene. Indeed, quantitative reverse transcriptase polymerase chain reaction (RT-PCR) analysis showed that ABA or low fluence red light stimulated expression of Atpirin1. Analysis of atpirin1 mutants showed that they exhibited similar phenotypes to GPA1 mutants with respect to seed germination, including hypersensitivity to the delaying effects of ABA, consistent with these two proteins participating in seed germination signaling pathways. In vitro, the interaction between AtPirin1 and GPA1 was not dependent on the activation state of GPA1. AtPirin1 appears also to participate in GPA1-independent pathways, because atpirin1 mutants exhibited accelerated flowering rate, which is not a phenotype of the GPA1 mutants. It remains to be determined how GPA1 and AtPirin1 participate and interact during plant signaling. Y. R. Lapik, L. S. Kaufman, The Arabidopsis cupin domain protein AtPirin1 interacts with G protein α-subunit GPA1 and regulates seed germination and early seedling development. Plant Cell 15, 1578-1590 (2003). [Abstract] [Full Text]


Sahul, the combined landmass of Australia and New Guinea, provides a record of behavioural modernity extending over at least the last 50,000 years. Colonised solely by anatomically and behaviourally modern humans, this continent provides an alternative record in the investigation of behavioural modernity to the extensively studied Middle Stone Age African and Upper Palaeolithic Eurasian archaeological records. In the past, the archaeological record of behavioural modernity in Sahul has been described as simple, sparse and essentially different to those records of Africa and Eurasia. These differences have been attributed to either low population densities during the Pleistocene or the loss of behavioural 'traits' on the journey from Africa to Sahul. While a number of studies have been undertaken, no single researcher has attempted to investigate the role of taphonomy and sampling on the representation of behavioural modernity in the archaeological record, despite Sahul being characterised by extreme environments, highly variable climates, and archaeologically, usually only small excavations. This study compiles the most complete record of chronology, evidence for behavioural modernity and excavation details for 223 Pleistocene sites yet attempted. It is also the most extensive dataset assembled for the examination of the issue of behavioural modernity on a single landmass. Site spatial and temporal distribution, site characteristics, excavations, absolute dating, preservation and sample size are examined to determine how the behavioural complexity of a modern human population is characterised on this isolated southern continent and the impact of taphonomy and archaeological sampling on that representation. Results demonstrate that preservation and sampling play a significant role in structuring the spatial and temporal representation of behavioural modernity in the archaeological record of Pleistocene Sahul. Contrary to previous findings, the evidence for behavioural modernity in Sahul is found to resemble the archaeological records of the African Middle Stone Age and Eurasian Upper Palaeolithic in terms of behaviour and artefact diversity. In terms of global narratives, these results also indicate that current understandings of behavioural modernity are incomplete and may misrepresent levels of behavioural complexity in early periods in some regions.


The folowing master thesis has focused on the optimisation and analysis of fixed
mounting systems for solar parks. It has been done in colaboration with Hilti Corp., one of
the most important designers and producers of fixed mounting systems for solar power farms
worldwide.
The current paper compares two existing Hilti's fixed mounting systems each of them
made of different material. This comparison shows the differences between two products
with the same flexibility, ease of mounting and design concept but made of different materials
and produced through different manufacturing processes.
At the same time, the analysis aims not to only compare but also to find the optimum
utilization point for both systems, in terms of span and cost. The span, or the distance
between two support structures determines significantly the output cost of the system overal.
As a result the "optimum span" has been also a target of the study.
Al the results found have been based on a cost model designed within Hilti specialy for
this report which embraces, concurrently, al load data calculated by other Hilti software and
other hot topics with regards to design. Although plenty of load calculations and redesigning
have been done the ultimate tool used has been the mentioned cost model.
This powerful tool has permitted the comparison of both fixed mounting systems in terms
of costs, performance and optimisation. Nevertheless, the three concepts just mentioned are
aforementioned and they can be described using a performance ratio given by the cost
model. This ratio which relates the system cost with the power output from the instalation
and has been used as the main assessment variable is Euro/Wp.
Thus, a comparison valid not only in the engineering field but also in the marketing can
be obtained from the model drawing conclusion whether it is better to design a fixed
mounting system for solar parks in aluminium or steel and what are their optimum utilisation
points.


MicroRNAs (miRNAs) play key roles in mammalian folliculogenesis (a complex process in which primordial follicles develop into mature oocytes) by inhibiting mRNA translation or by inducing its degradation, while the role of miRNA in folliculogenesis and regulation mechanism remain unclear. In this study, we explored the role of the p53/miR-27a/nuclear factor of activated T-cells 5 (NFAT5) signaling axis in mouse ovarian granulosa cell proliferation. Luciferase reporter assay, overexpression, site-directed mutagenesis, and chromatin immunoprecipitation (ChIP) assay results showed that the transcription factor p53 significantly decreased the expression level of miR-27a by binding to sites 4 (-646 to -637 bp) and 10 (-50 to -41 bp) of the miR-27a promoter. Moreover, miR-27a directly targeted the 3′-untranslated region of the target gene, NFAT5, to regulate its expression levels. p53 also upregulated the expression of NFAT5. Meanwhile, overexpression of NFAT5 strongly upregulated the mRNA and protein levels of the Wnt signaling genes, β-catenin and B-Cell CLL/Lymphoma 2 (Bcl-2). In addition, NFAT5 promoted mouse granulosa cell proliferation; this was confirmed by EdU/Hoechst immunostaining. Taken together, our findings define a novel pathway p53/miR-27a/NFAT5, and NFAT5 regulates mouse granulosa cell functions via activating Wnt signaling pathway.


Abstract. A statistical study is presented of the unstable proton populations, which contain the free energy required to drive small-scale poloidal mode ULF waves in the magnetosphere, observed at invariant latitudes of 60° to 80°. The data are all in the form of Ion Distribution Functions (IDFs) amassed over ~6 years using the CAMMICE (MICS) instrument on the Polar spacecraft, and cover proton energies of 1 keV to 328 keV. The free energy contained in the unstable, positive gradient regions of the IDFs is available to drive resonant wave growth. The results show that positive gradient regions in IDFs on magnetic field lines corresponding to the lower invariant latitudes in the range under study occur predominantly in the afternoon sector at proton energies of 5 keV to 20 keV. In the morning and dawn sectors positive gradient regions are seen with a typical proton energy range of 5 keV to 45 keV. While the proton energy peaks in the afternoon sector at around ~7 keV the morning sector has two peaks occurring at ~10 keV and ~20–30 keV. The technique of Baddeley et al. (2004), employed to quantify the free energy in each IDF, found that as invariant latitude increased the free energy contained in the positive gradient regions fell. Positive gradient regions in the afternoon sector decrease in number with invariant latitude at a faster rate than those in the morning sector. The majority of positive gradient regions had free energy values of >1010 J with many at the lowest invariant latitudes having free energies of in excess of 1011 J. Positive gradient regions at proton energies of >100 keV are rarely observed, and have free energies of typically


Natural killer (NK) cells are involved in graft rejection and may contribute to tumor recognition and elimination. Ogasawara et al. report that increased production of NKG2D ligands may be one mechanism by which certain tissues are prone to graft rejection and that antibodies against NKGD2 can prevent rejection in these cases. Oppenheim et al. report that localized high expression of NKG2D ligands inhibited NK cell function, contributing to evasion of the immune system by tumors. To study graft rejection, Ogasawara et al. evaluated NKG2D ligand expression (by antibody staining) of bone marrow cells from BALB/C or C57BL/6 mice that were transplanted into irradiated F1 progeny from a BALB/C C57BL/6 cross, an example of F1 hybrid resistance. The BALB/C cells expressed the ligand Rae-1 and were rejected by the F1 progeny mice. The C57BL/6 mouse cells were also rejected, but they did not express any NKG2D ligands; thus, there are at least two mechanisms for NK cell-mediated rejection. Depletion of the NK cells from the recipient mice allowed the transplanted cells from both parental strains to survive; however, only in the case of the BALB/C transplanted cells did neutralizing antibodies to NKG2D increase the incorporation of the transplanted cells in the spleens of the recipient mice. The Rae-1 ligand was also the focus of the studies by Oppenheim et al. In this case, two kinds of transgenic mice were generated: those expressing Rae-1ε in squamous epithelium only (lines 110 and 121) and those expressing Rae-1ε ubiquitously (line 187). Both types of transgenic mice showed decreased abundance of NKG2D-positive NK cells; however, the abundance of other proteins (such as CD94) typically expressed by this population of NK cells was normal. Thus, the NKG2D receptor itself appeared to be down-regulated rather than the cell population depleted. Coculturing of NKG2D-positive splenocytes with the splenocytes from the 187 line (high Rae-11ε) resulted in loss of NKG2D from the nontransgenic cells. Injection of a mixture of splenocytes from the 187 line and control splenocytes into control mice or transgenic mice showed that clearance of the Rae-1-positive cells was impaired in the transgenic mice. Activation of the NK cells with poly (I:C) restored killing of the Rae-1-positive cells in the epithelial transgenic mice only, suggesting that a residual population of NKG2D-positive cells could be rescued in the 110 and 121 lines. Finally, the transgenic mice showed increased susceptibility to tumorigenesis (chemical induced and injection of tumor cells). Thus, the NKG2D receptor is a critical player in tumor surveillance and graft rejection. K. Ogasawara, J. Benjamin, R. Takaki, J. H. Phillips, L. L. Lanier, Function of NKG2D in natural killer cell-mediated rejection of mouse bone marrow grafts. Nat. Immunol. 6, 938-945 (2005). [Online Journal] D. E. Oppenheim, S. J. Roberts, S. L. Clarke, R. Filler, J. M. Lewis, R. E. Tigelaar, M. Girardi, A. C. Hayday, Sustained localized expression of ligand for the activating NKG2D receptor impairs natural cytotoxicity in vivo and reduces tumor surveillance. Nat. Immunol. 6, 928-937 (2005). [Online Journal]