The theory of integral quadratic constraints (IQCs) allows the certification of exponential convergence of interconnected systems containing nonlinear or uncertain elements. In this work, we adapt the IQC theory to study first-order methods for smooth and strongly-monotone games and show how to design tailored quadratic constraints to get tight upper bounds of convergence rates. Using this framework, we recover the existing bound for the gradient method~(GD), derive sharper bounds for the proximal point method~(PPM) and optimistic gradient method~(OG), and provide \emph{for the first time} a global convergence rate for the negative momentum method~(NM) with an iteration complexity $\bigo(\kappa^{1.5})$, which matches its known lower bound. In addition, for time-varying systems, we prove that the gradient method with optimal step size achieves the fastest provable worst-case convergence rate with quadratic Lyapunov functions. Finally, we further extend our analysis to stochastic games and study the impact of multiplicative noise on different algorithms. We show that it is impossible for an algorithm with one step of memory to achieve acceleration if it only queries the gradient once per batch (in contrast with the stochastic strongly-convex optimization setting, where such acceleration has been demonstrated). However, we exhibit an algorithm which achieves acceleration with two gradient queries per batch.


A thesis submitted in partial fulfillment of the requirements for the award of the Master of Medicine Degree of Makerere University.


Since my first book, Modernism, the Market and the Institution of the New, I've been interested in the question of generations, particularly in that volume aiming to assess the tensions between high modernists and late modernists on matters of innovation and cultural positioning from about 1926. Of particular interest to me was the question as to how far the high modernists had become institutionalized as a group and how far those who arrived in their wake (so-called second-generation modernists) had to deal with an institutionally- or popularlyestablished conception of the movement. My next project engages with similar questions of literary history and the established conceptions of the movement arising in the period – pursuing the question, as you ask in the CFP, 'Are Modernists aware of themselves as modernists?' – by examining in detail the literary memoirs written by modernist artists, writers, publishers, journalists and their friends published between 1929 and 1969. These books often aim to not only assert an individual's narrative within literary or art history, but to write the narrative of the movement itself – sometimes under the burden of significant personal agendas or ambitions. I would like to present findings from this ongoing research into modernist memoirs at the 'Generation M' conference, particularly that arising from the literary historical formulations constructed by these authors as they relate to generations and age groups. Some of the more impressionable terms we continue to use in literary histories, including 'the men of 1914' and 'the lost generation', were proposed and elaborated in literary memoirs. In 1934, Malcolm Cowley writes about the role of a young writer reading from 'the Lives of the Saints', by which he means the older generation (including high modernists like Joyce and Eliot) – finding them, ultimately, insufficient as guides for the younger generation's problems. In 1937, Wyndham Lewis writes about this same 'Age Group' and its origins – as he aims to 'fix for an alien posterity' that which the previous generation called, in the words of Ford Madox Ford, a 'haughty and proud generation'. These two texts, alone, raise questions about where the lines can be drawn within and around modernist generations. But later memoirs add context as well. Hemingway, in 1964, would exfoliate his own 1926 use of the phrase 'a lost generation' after it had built up a literary historical definition of its own (even Strauss and Howe use 'the lost generation' as signifier for an entire American age group in their influential Generations) – remembering the unfairness of the attack on his own generation by those of the older generation, and seeking to hold them accountable for their own failures. And in one of the last modernist memoirs to be published, John Glassco remembers visiting George Moore in London on his way to Paris, and confiding to the 87 yearold novelist that The Confessions of a Young Man (1886) is one of his favourites. Moore thinks readers must 'look on that as dated … nowadays', but Glassco's companion asserts to the contrary, 'It will never date, it's a kind of statement of youth for all time' – and it is this which leads Glassco to focus on his own memoirs rather than poetry while in Paris. In passages like these, it becomes clear just how far memoir is a tool for asserting a version of one's own modernity – for narrating one's belonging to one's period and establishing its place within literary traditions. Particularly the notion of creating a statement of youth (could we say 'modernity'?) 'for all time' is a subject to be examined as the memoirists seek to place their own work and their own time both against the backdrop of a previous generation and as a legacy for the coming generations, establishing their own literary historical narratives and shaping its contours.


This paper contains the results of a study of human remains—artifacts, workshops, camp sites, and hearths—and of the associated animals found in the Berclair terrace deposits of the Mission River drainage system of the Coastal Plain region of Texas. The artifacts are referable to Folsom, Yuma, and cultures known from central Texas, and some are not definitely placed as to cultural position. The Folsom and Yuma cultures are found near the base of the deposit; the central Texas culture occurs in the upper part but may likewise extend to the lower levels. The extinct mammals of the formation include mammoth, mastodon, horse, bison, camel, dire wolf, peccary, armadillo, glyptodon, and ground sloth. There are also some extinct turtles of which the species have not been determined.

Since deposition of the terrace, regional uplift has rejuvenated the streams which have now become intrenched in the Berclair terrace deposits. Due to this uplift the present streams have a steeper gradient than the earlier streams. On stratigraphic evidence the Berclair terrace deposits are shown to be the upstream equivalent of the Beaumont formation, probably of Lower Beaumont age. The correlation, as indicated by the vertebrate fossils, is with the Melbourne formation of Florida and almost, if not exactly, with the Tedford bone bed of San Patricio County, Texas. The paleontologic and stratigraphic evidence indicates that the formation and the included artifacts and fossils are Pleistocene.

The fact that man inhabited these valleys during the Pleistocene implies, consistent with other evidence, that he had then attained a wide distribution on the continent. The varied and specialized cultural development of the Mission River valley inhabitants suggests that this occurrence does not represent the earliest occurrence of man in North America. The time of arrival of man on the continent is yet to be determined.


This paper presents the use of Weibull formulation to the life analysis of different parts of the engine in order to estimate the cost of maintenance, the direct operating costs (DOC) and net present cost (NPC) of future type turbofan engines. The Weibull distribution is often used in the field of life data analysis due to its flexibility—it can mimic the behavior of other statistical distributions such as the normal and the exponential. The developed economic model is composed of three modules: a lifing module, an economic module and a risk module. The lifing module estimates the life of the high pressure turbine blades through the analysis of creep and fatigue over a full working cycle of the engine. The value of life calculated by the lifing is then taken as the baseline distribution to calculate the life of other important modules of the engine using the Weibull approach. Then the lower of the values of life of all the distributions is taken as time between overhaul (TBO), and used into the economic module calculations. The economic module uses the TBO together with the cost of labour and the cost of the engine (needed to determine the cost of spare parts) to estimate the cost of maintenance and DOC of the engine. In the present work five Weibull distributions are used for five important sources of interruption of the working life of the engine: Combustor, Life Limited Parts (LLP), High Pressure Compressor (HPC), General breakdowns and High Pressure Turbine (HPT). The risk analysis done in this work shows the impact of the breakdown of different parts of the engine on the NPC and DOC, the importance that each module of the engine has in its life, and how the application of the Weibull theory can help us in the risk assessment of future aero engines. A detailed explanation of the economic model is done in two other works (Pascovici et. al. [6] and Pascovici et. al. [7]), so in this paper only a general overview is done.


A total of 124 delicatessen meat products were analysed for microbiological quality shortly after purchase and following storage at 22 C for 24 h. Sixty-seven of these products were portion packages and 57 were cuts from bulk products. Coliforms, coagulase-positive staphylococci and Clostridium perfringens contamination was low. Salmonella was not detected in any of the samples. Initially, 34.3% of the portion-packed and 24.5% of bulk cuts contained more than 107 total aerobic plate count per g and, following storage this proportion increased to 62.7% and 57.9%, respectively. Eight samples (11.9%) of portion-packed and seven samples (12.3%) of bulk cuts contained more than 107 psychrotrophs per g initially. After storage, 35% of both types of products yielded >107 psychrotrophs per g. Significant levels of fecal streptococci and yeasts were also isolated from many of these products, indicating need for improvement in manufacturing procedures and retail storage conditions. However, the results of this investigation indicated that chances of a public health hazard from delicatessen meat products would be low.


Remanufacturing restores used automotive engines to like‐new condition, providing engines that are functionally equivalent to a new engine at much lower environmental and economic costs than the manufacture of a new engine. A life‐cycle assessment (LCA) model was developed to investigate the energy savings and pollution prevention that are achieved in the United States through remanufacturing a midsized automotive gasoline engine compared to an original equipment manufacturer manufacturing a new one. A typical full‐service machine shop, which is representative of 55% of the engine remanufacturers in the United States, was inventoried, and three scenarios for part replacement were analyzed. The life‐cycle model showed that the remanufactured engine could be produced with 68% to 83% less energy and 73% to 87% fewer carbon dioxide emissions. The life‐cycle model showed significant savings for other air emissions as well, with 48% to 88% carbon monoxide (CO) reductions, 72% to 85% nitrogen oxide (NOx) reductions, 71% to 84% sulfur oxide (SOx) reductions, and 50% to 61% nonmethane hydrocarbon reductions. Raw material consumption was reduced by 26% to 90%, and solid waste generation was reduced by 65% to 88%. The comparison of environmental burdens is accompanied by an economic survey of suppliers of new and remanufactured automotive engines showing a price difference for the consumer of between 30% and 53% for the remanufactured engine, with the greatest savings realized when the remanufactured engine is purchased directly from the remanufacturer.


As numerous transport infrastructure projects have been implemented, recent years have witnessed a significant increase in transport network in urban and regional areas. A number of studies have been undertaken to examine whether transport improvement impacts commercial property values and have found that proximity to public transits leads to an increase in rental values of commercial properties. Few studies, however, have focused on investigating the relationship between change in accessibility and commercial property values with a longitudinal analysis. This study therefore seeks to investigate how change in accessibility impacts commercial property retail values. A gravity-type accessibility indicator will be developed in order to enhance the measurement of accessibility in the analysis. This accessibility will gauge accessibilities of commercial properties to the market potential for two time points: 2000 and 2010. Drawing on that accessibility indicator and commercial property attributes collected from private companies, this study will develop a longitudinal econometric model to analyze the impact of the change in accessibility on commercial property rental values. A hypothesis to be tested is that an increase in accessibility does not lead to a rise in rental values of commercial properties.


Purpose: Catheter-directed thrombolysis (CDT) is a relatively new therapy for pulmonary embolism that achieves the superior clot resolution compared to systemic thrombolysis while avoiding the high bleeding risk intrinsically associated with that therapy. In order to examine the efficacy and safety of CDT, we conducted a retrospective cohort study of patients undergoing ultrasound-assisted CDT at our institution. Methods: The charts of 30 consecutive patients who underwent CDT as a treatment of pulmonary embolism at our institution were reviewed. Risk factors for bleeding during thrombolysis were noted. Indicators of the right heart strain on computed tomography and echocardiogram, as well as the degree of pulmonary vascular obstruction, were recorded before and after CDT. Thirty-day mortality and occurrence of bleeding events were recorded. Results: Nine (30%) patients had 3 or more minor contraindications to thrombolysis and 14 (47%) had major surgery in the month prior to CDT. Right ventricular systolic pressure and vascular obstruction decreased significantly after CDT. There was a significant decrease in the proportion of patients with right ventricular dilation or hypokinesis. Decrease in pulmonary vascular obstruction was associated with nadir of fibrinogen level. No patients experienced major or moderate bleeding attributed to CDT. Conclusion: Catheter-directed thrombolysis is an effective therapy in rapidly alleviating the right heart strain that is associated with increased mortality and long-term morbidity in patients with pulmonary embolism with minimal bleeding risk. Catheter-directed thrombolysis is a safe alternative to systemic thrombolysis in patients with risk factors for bleeding such as prior surgery. Future studies should examine the safety of CDT in patients with contraindications to systemic thrombolysis.


A palaeomagnetic study has been conducted to examine the deformation of thick crusts of rhyolite lava while its inner portions continue to flow. The Sanukayama rhyolite lava, which erupted in the Pleistocene in Kozushima Island, Japan, was chosen as the investigation site because of its well-exposed vertical lithofacies variations classified into three distinct zones (pumiceous, obsidian and crystalline). The targets of this study are the pumiceous and obsidian zones, which constitute the crust of the lava. Thermal demagnetization reveals three remanent magnetization components from the pumiceous and obsidian samples but only a single magnetization component from the inner crystalline rhyolite samples. Alternating field demagnetization is ineffective in isolating the magnetization components in the pumiceous and obsidian samples. The multiple components of remanent magnetization of the crust are interpreted to have been acquired during cooling as thermoremanent magnetizations. We suspect intermittent lava transport of the inner portions, the primary mode of rhyolite lava advancement, to be responsible for the presence of multiple components in pumice and obsidian of the lava crust. When the inner portions of the lava retain mobility to flow out of the crust, the solidified crust of the lava surface below the magnetite Curie temperature remains susceptible to deformation. Analysis of palaeomagnetic directions from the crust allows the deformation of the crust to be described in terms of rotation. Although the mode of rhyolite lava advancement is not well understood, because of its infrequent occurrence, our observations offer an important insight on how the mobile part of the lava is associated with the deformation of the crust during continued lava advance.


The origin and development of the nomina sacra (sacred names written in an abbreviated form) found in early Christian texts is much debated in scholarly circles and no agreement has been reached. However the use of the nomina sacra in P.Lond.Lit. 207 may help to resolve some of the questions that surround the puzzle of their origin. P.Lond.Lit. 207 is a portion of papyrus that has broken off from a roll (24.5 X 25.7 cm), covering Psalms 11(12):7 to 14(15):4. The scribe of P.Lond.Lit. 207 has consistently written Kurios in an abbreviated form ( nomen sacrum ), giving only the first and last letters, and a supralinear bar drawn above the abbreviation. On the other hand, Theos is always written uncontracted. This is quite unusual given that Theos in Christian texts is always written as a nomen sacrum . Could the reason for this practice in P.Lond.Lit. 207 be found in the Semitic custom of contracting personal names to the first and last letter? Is Kurios abbreviated in this Semitic fashion to notify the reader that the word is being used to translate the personal name (the Tetragrammaton) of the Hebrew deity?


Provision of safe water for consumption and appropriate sanitation facilities have variously been advocated as critical forerunners to pupil participation in primary school education. However, these facilities are not consistently provided, that in various schools, water and cleanliness services are in dilapidated condition and thus expose pupils to obvious health risk and unsafe learning environments. This study investigated the access to clean water for drinking and sanitary facilities and pupil participation in education in public primary schools in Gichugu Constituency, Kirinyaga County, Kenya. The objectives of the study were to; assess the relationship between availability to safe drinking, establish the provision of sanitation facilities and pupil participation in public primary schools. The research design used in this study was the descriptive survey and the theory that guided it was the Social Constructionist of Sahlin. The target population covered 75 head teachers in public primary schools in Gichugu Constituency. Krecjie and Morgans formula was used in sample size determination which yielded a sample of 63 respondents and simple random sampling to select the study sample. A self-scoring questionnaire administered to the sampled respondents was used to collect data. Descriptive statistics, namely frequencies and percentages were used in data analysis and was aided the computer software SPSS version 20. The findings were represented in form of frequency tables and narrations. The research revealed that most schools had hygienic and water for drinking available to the learners. The study also revealed that academic participation improved in schools where pupils had hygienic drinking water, while absence of clean water for drinking led to poor school. The study established that poor sanitation amenities led to occurrence of infections which affected learners' participation in curricular activities. Lack of clean conveniences added to absenteeism and high occurrences of diseases among pupils in primary schools. In line with the findings, the study commends that the, National and County Governments and the local community should ensure that all public primary schools in Gichugu Constituency have been supplied with piped water in order to control infections that affect pupils' attainment of education. Education stakeholders ought to underscore the provision of adequate sanitation facilities schools so as to advance pupils' hygiene and participation in school


Objectives: To identify the predominance of Total Quality Management (TQM) practices in small and medium sized manufacturing companies in the Philippines and its relationship to financial performance. Methods: Questionnaires were administered among the owners/managers of the 50 small and medium manufacturing firms which were chosen through multi-stage random sampling. The questionnaire was composed of questions relating to quality practices in terms of management commitment and leadership, continuous improvement, total customer satisfaction, employee involvement, education and training, and reward and recognition. Descriptive statistics and Pearson Product Moment of Correlation were used to analyse the data in the study. Findings: The results reveal that the TQM practices in terms of management leadership and commitment, customer satisfaction, and continuous improvement are highly predominant while employee involvement, training and education, and rewards and recognition are only moderately predominant. Furthermore, aside from continuous improvement which was found to have a significant relationship to the solvency of the companies, there was no significant relationship between the other areas of TQM and the financial performance of the companies in terms of liquidity, solvency and profitability. These results run parallel with the fact that the rewards of TQM are highly long-range which means that any investment in the quality efforts now may not necessarily lead to any positive improvement in financial performance at once, or in the short term. This is the reason why there is a high degree of management commitment necessary in order to keep the improvement efforts afloat. This study has produced an important insight that a long-term dedicated SME quality development campaign can be an ideal strategy to improve productivity. Improvements: A comparison on the adoption of TQM between companies in terms of time period would give insights of the effects of TQM, if any, when conducted over long-term.
Keywords: Profitability, Quality, Small and Medium Enterprise, Total Quality Management


A 48‐year‐old man with severe, lifelong Tourette's syndrome (TS) characterized by forceful self‐injurious motor tics and obsessive‐compulsive disorder was treated with bilateral deep brain stimulation (DBS). The decision to treat was based on his progressive neurological impairment (left sided weakness secondary to spinal cord injury) because of his relentless, violent head jerks. Electrodes were implanted at the level of the medial part of the thalamus (centromedian nucleus, the substantia periventricularis, and the nucleus ventro‐oralis internus). DBS resulted in a substantial reduction of tics. These data show that bilateral DBS of the thalamus can have a good effect on severe tics in adult patients suffering from intractable TS. © 2007 Movement Disorder Society


The mucus layers on the internal surfaces of the human body serve as an important barrier against foreign material, but it also create restrictions regarding drug delivery. Discovering methods to overcome this barrier would lead us closer to an efficient delivery of larger drugs and nanoparticles. Recent studies have shown that alginate G-block polymers can modify the physical properties of mucus, and that the G-blocks make the mucin network more open and increase particle transport through mucus. This shows that G-blocks are an interesting candidate, for use in drug delivery across mucosal barriers, but further work to understand the mechanisms by which the G-blocks interact with mucus is still desirable. Studies have shown that neutral particles diffuse more easily through mucus than charged particles. In this thesis the interactions between nanoparticles with different surface structures and mucus components were compared by dynamic light scattering and the effect of G-block on these interactions was established. The diffusions of all particle types were compared in pig gastric mucin (PGM) from Sigma, by the use of confocal microscopy and multiple particle tracking (MPT). Then alginate G-blocks were added and the diffusion of the particle types was compared. The results showed that G-blocks can reduce the amount of mucin components accumulating on to positively charged surfaces but not to negatively charged particles. The MPT showed that the surface charge of the nanoparticles is the primary determining factor when it comes to diffusion through Sigma mucin, and that the effect on the diffusions caused by G-blocks is relatively small, most probably due to the matrix of Sigma mucin, lacking the large networking polymers on which G-blocks previously have shown their effect. It was found that G-blocks make the distribution of trajectories more homogenous, but that this did not affect the mean displacements.


We identify and explore an Information Retrieval paradigm called Query-By-Multiple-Examples (QBME) where the information need is described not by a set of terms but by a set of documents. Intuitive ideas for QBME include using the centroid of these documents or the well-known Rocchio algorithm to construct the query vector. We consider this problem from the perspective of text classification, and find that a better query vector can be obtained through
learning with Support Vector Machines (SVMs). For online queries, we show how SVMs can be learned from one-class examples in linear time. For offline queries, we show how SVMs can be learned from positive and unlabeled examples together in linear or polynomial time, optimising some meaningful multivariate performance measures. The effectiveness and efficiency of the proposed approaches have been confirmed by our experiments on four real-world
datasets.


The battery management system (BMS) is a critical component of electric vehicles. The purpose of the BMS is to guarantee safe and reliable battery operation. To maintain the safety and reliability of the battery, state monitoring and evaluation, charge control, and cell balancing are functionalities that have been implemented in BMS. As an electrochemical product, a battery acts differently under different operational and environmental conditions. The uncertainty of a battery's performance poses a challenge to the implementation of these functions. This paper addresses concerns for current BMSs. State evaluation of a battery, including state of charge, state of health, and state of life, is a critical task for a BMS. Through reviewing the latest methodologies for the state evaluation of batteries, the future challenges for BMSs are presented and possible solutions are proposed as well.


The spraying of coca (Erythroxylum coca) with glyphosate (coca mixture, a combination of formulated glyphosate, Glyphos, and an adjuvant, Cosmo-Flux) in Colombia has raised concerns about possible impacts on amphibians. Although acute LC50 for 8 species of Colombian frogs ranged from 1.2 to 2.78 mg acid equivalents (a.e.)/L, these exposures were conducted in the laboratory in the absence of sediments and organic matter such as would occur under realistic field conditions. In order to assess the effects of overspray of frog habitat under field conditions, Gosner stage 25 tadpoles of Rhinella granulosa, R. marina, Hypsiboas crepitans, and Scinax ruber were placed in outdoor microcosms made from polyethylene plastic fish ponds (2.07 m in diameter, 37 cm high) in an experimental area in Tolima, Colombia. The bottoms of the microcosms were covered with a 3-cm layer of local soil and they were filled to a depth of 15 cm (above the sediment) with local spring water. After up to 100 tadpoles of each frog species were placed in the microcosms, they were sprayed with the coca mixture at concentrations greater and less than the normal application rate (3.69 kg glyphosate a.e./ha). Mortality at 96 h in the control microcosms was between 0 and 16% and LC50 values were between 8.9 and 10.9 kg glyphosate a.e./ha (equivalent to initial concentrations of 5963 to 7303 μg glyphosate a.e./L). Mortality >LC50 was only observed in the tested species when the application rate was >2-fold the normal application rate. In other experiments, juvenile and adult terrestrial stages of frogs were exposed by direct spraying to a range of concentrations of coca mixture. Juveniles and adults were exposed in plastic food containers (19 × 19 cm). The bottom of the container was filled with moistened soil and leaf litter to a depth of 1 cm and 0.5 cm, respectively. Mortality in the controls was low, from 0 to 10%, and from 0 to 35% at the normal application rate. LC50 values ranged between 4.5 kg a.e./ha and 22.8 kg a.e./ha, 1.5- to 6-fold greater than the normal application rate. Data indicate that, under realistic worst-case exposure conditions, the mixture of Glyphos and Cosmo-Flux as used for control of coca in Colombia exerts a low toxicity to aquatic and terrestrial stages of anurans and that risks to these organisms under field conditions are small.


Connexin32 (Cx32) mutants were studied by double voltage clamp in Xenopus oocytes to determine the role of basic COOH-terminal residues in gap junction channel gating by CO2 and transjunctional voltage. Replacement of five arginines with N (5R/N) or T residues in the initial COOH-terminal domain (CT1) of Cx32 enhanced CO2 sensitivity. The positive charge, rather than the R residue per se, is responsible for the inhibitory role of CT1, because mutants replacing the five R residues with K (5R/K) or H (5R/H) displayed CO2 sensitivity comparable to that of wild-type Cx32. Mutants replacing R with N residues four at a time (4R/N) showed that CO2 sensitivity is strongly inhibited by R215 and mildly by R219, whereas R220, R223, and R224 may slightly increase sensitivity. Neither the 5R/N nor the 4R/N mutants differed in voltage sensitivity from wild-type Cx32. The possibility that inhibition of gating sensitivity results from electrostatic interactions between CT1 and the cytoplasmic loop is discussed as part of a model that envisions the cytoplasmic loop of Cx32 as a key element of chemical gating.


OBJECTIVE
Osteoarthritis (OA) is a degenerative disease resulting in severe joint cartilage destruction and disability. While the mechanisms underlying the development and progression of OA are poorly understood, gene mutations have been identified within cartilage-related signaling molecules, implicating impaired cell signaling in OA and joint disease. The Notch pathway has recently been identified as a crucial regulator of growth plate cartilage development, and components are expressed in joint tissue. This study was undertaken to investigate a novel role for Notch signaling in joint cartilage development, maintenance, and the pathogenesis of joint disease in a mouse model.

METHODS
We performed the first mouse gene study in which the core Notch signaling component, RBP-Jκ, was tissue specifically deleted within joints. The Prx1Cre transgene removed Rbpjk loxP-flanked alleles in mesenchymal joint precursor cells, while the Col2Cre(ERT2) transgene specifically deleted Rbpjk in postnatal chondrocytes. Murine articular chondrocyte cultures were also used to examine Notch regulation of gene expression.

RESULTS
Loss of Notch signaling in mesenchymal joint precursor cells did not affect embryonic joint development in mice, but rather, resulted in an early, progressive OA-like pathology. Additionally, partial loss of Notch signaling in murine postnatal cartilage resulted in progressive joint cartilage degeneration and an age-related OA-like pathology. Inhibition of Notch signaling altered the expression of the extracellular matrix (ECM)-related factors type II collagen (COL2A1), proteoglycan 4, COL10A1, matrix metalloproteinase 13, and ADAMTS.

CONCLUSION
Our findings indicate that the RBP-Jκ-dependent Notch pathway is a novel pathway involved in joint maintenance and articular cartilage homeostasis, a critical regulator of articular cartilage ECM-related molecules, and a potentially important therapeutic target for OA-like joint disease.


Translation Lookaside Buffers, or TLBs, play a vital role in recent microarchitectural attacks. However, unlike CPU caches, we know very little about the exact operation of these essential microarchitectural components. In this paper, we introduce TLB desynchronization as a novel technique for reverse engineering TLB behavior from software. Unlike previous efforts that rely on timing or performance counters, our technique relies on fundamental properties of TLBs, enabling precise and fine-grained experiments. We use desynchronization to shed new light on TLB behavior, examining previously undocumented features such as replacement policies and handling of PCIDs on commodity Intel processors. We also show that such knowledge allows for more and better attacks. Our results reveal a novel replacement policy on the L2 TLB of modern Intel CPUs as well as behavior indicative of a PCID cache. We use our new insights to design adversarial access patterns that massage the TLB state into evicting a target entry in the minimum number of steps, then examine their impact on several classes of prior TLB-based attacks. Our findings enable practical side channels à la TLBleed over L2, with much finer spatial discrimination and at a sampling rate comparable to L1, as well as an even finer-grained variant that targets both levels. We also show substantial speed gains for other classes of attacks that rely on TLB eviction.


From an analysis of the sky and velocity distributions of the high-velocity clouds (HVCs) we show that the majority of the HVCs has a common origin. We conclude that the HVCs surround the Galaxy, forming a metacloud of ∼300 kpc in size and with a mass of ∼3 × 10 9 M� , and that they are the product of a powerful "superwind" (about 10 58 ergs), which occurred in the Magellanic Clouds about 570 Myr ago as a consequence of the interaction of the Large and Small Magellanic Clouds. The HVCs might be magnetic bubbles of semi-ionized gas, blown from the Magellanic Clouds around 570 Myr ago, that circulate largely through the halo of the Galaxy as a stream or flow of gas. On the basis of the connection found between the HVCs and the Magellanic Clouds, we have constructed a theoretical model with the purpose of computing the orbits of a sample of test particles representing the HVCs, under the gravitational action of the Galaxy and the Magellanic Clouds. The orbits of the Large and Small Magellanic Clouds have been traced backwards in time to estimate the position and velocity of the Clouds at the time of the collision between the two Clouds, and to infer the initial conditions of the HVCs. The model can reproduce the main features of position and velocity distributions of the HVCs, like the overall structure and kinematics of the Magellanic Stream. The initial velocities of the HVCs were the result of velocities of expansion that permitted the escape of the HVCs from the Magellanic Clouds plus the systemic velocity of the Magellanic Clouds at the time of the collision. With these initial conditions, the Galactic gravitational potential induced differential rotations or shearing motions that elongated the cloud of HVCs in the orbital direction, forming the rear and front parts of the Magellanic stream. The population of HVCs is centered around the Magellanic Clouds. The eccentric position of the Sun within the cloud of HVCs explains the asymmetries between the sky distributions of the HVCs of the northern Galactic hemisphere and those of the southern Galactic hemisphere. In the light of the model we analyze the effects that the passage of the HVC flow through the Galactic disk has produced on the interstellar medium. The effects of the HVC flow can account for many observational details such as the Galactic warp, HI shells and supershells in the gaseous layer of the outer parts of the Milky Way. The Galactic disk was target of numerous impacts of HVCs in the course of the last 400 Myr, accumulating mass at the average rate of approximately 0.6 Mper year. The events of this period may be regarded as landmarks in the evolutionary history of the Milky Way.


Abstract The probability of accepting a candidate move in the hybrid Monte Carlo algorithm can be increased by considering a transition to be between windows of several states at the beginning and end of the trajectory, with a particular state within the selected window then being chosen according to the Boltzmann probabilities. The detailed balance condition used to justify the algorithm still holds with this procedure, provided the start state is randomly positioned within its window. The new procedure is shown empirically to significantly improve the acceptance rate for a test system of uncoupled oscillators. It also allows expectations to be estimated using data from all states in the windows, rather than just states that are accepted.


We live in a 'corporate world' in which powerful business corporations shape and influence the activities of nation states, their national economies and their social relations. Varieties of Capitalism, Corporate Governance and Employees looks at what it is that moulds the activities of the corporations themselves? Do some societies have 'styles' of regulation that enable corporations to operate freely in the pursuit of certain interests, where others are more constrained? And, if so, are Australian companies more inclined to pursue the financial interests of shareholders and owners at the expense of employees and creditors? Corporate governance may be guided in the pursuit of particular interests by many influences, including law, politics, capital and labour and other pressure groups. How these competing pressures balance out varies enormously from state to state. Bringing together the original research by lawyers, political economists and industrial relations scholars, Varieties of Capitalism, Corporate Governance and Employees is a first Australian contribution to these complex issues.


BACKGROUND
Implementation science (IS) occupies a critical place in HIV/AIDS research, reflected by a scientific track ("Track E") at the biannual International AIDS Conference. IS seeks to identify health delivery strategies that cost-effectively translate the efficacy of evidence-based interventions for HIV prevention, testing, and treatment into impact on HIV incidence, quality of life, and mortality.

METHOD
We reviewed the content of Track E, and other presentations relevant to IS, at the 22nd International AIDS Conference held in Amsterdam in 2018. We identified key findings and themes and made recommendations for areas where the field can be strengthened by the 2020 meeting.

RESULTS
Trials of "treat all" strategies in Africa showed mixed evidence of effect. Innovations in HIV testing included expanding self-testing and index testing, which are reaching groups, such as men, where previously testing rates have been low. Adherence clubs and other innovations are being trialed to improve retention in care, with mixed findings. The implementation of pre-exposure prophylaxis for HIV prevention continues but with many challenges remaining in identifying implementation strategies that strengthen demand and support continuation.

DISCUSSION
IS for HIV/AIDS treatment and prevention continues to expand. IS for primary HIV prevention must be prioritized with a dearth of rigorous, intersectoral studies in this area. The weakness of routine data must be addressed. Costing and financing studies should form a stronger component of the conference agenda. Implementation scientists must continue to grapple with the methodological challenges posed by the real-world context for their research.


Introduction The COVID-19 pandemic has posed major challenges to all aspects of healthcare. Malta's population density, large proportion of elderly and high prevalence of diabetes and obesity put the country at risk of uncontrolled viral transmission and high mortality. Despite this, Malta achieved low mortality rates compared to figures overseas. The aim of this paper is to identify key factors that contributed to these favorable outcomes. Methods This is a retrospective, observational, nationwide study which evaluates outcomes of patients during the first wave of the pandemic in Malta, from the 7th of March to the 24th of April 2020. Data was collected on demographics and mode of transmission. Hospitalization rates to Malta's main general hospital, Mater Dei Hospital, length of in-hospital stay, intensive care unit admissions and 30-day mortality were also analyzed. Results There were 447 confirmed cases in total; 19.5% imported, 74.2% related to community transmission and 6.3% nosocomially transmitted. Ninety-three patients (20.8%) were hospitalized, of which 4 were children. Patients with moderate-severe disease received hydroxychloroquine and azithromycin, in line with evidence available at the time. A total of 4 deaths were recorded, resulting in an all-cause mortality of 0.89%. Importantly, all admitted patients with moderate-severe disease survived to 30-day follow up. Conclusion Effective public health interventions, widespread testing, remote surveillance of patients in the community and a low threshold for admission are likely to have contributed to these favorable outcomes. Hospital infection control measures were key in preventing significant nosocomial spread. These concepts can potentially be applied to stem future outbreaks of viral diseases. Patients with moderate-severe disease had excellent outcomes with no deaths reported at 30-day follow up.


Space-time code (STC) designs commonly rely on the assumptions of independent and identically distributed (i.i.d.) Rayleigh channels (being either slow or fast fading) and high signal-to-noise ratio (SNR). However, it has been shown that poor scattering conditions can have detrimental effects on the performance of STCs and that the behavior of codes at high SNR is radically different from the finite SNR behavior. This calls for new design criteria that correctly predict the behavior of codes in correlated channels at finite SNR. In this paper, we investigate how spatially and temporally correlated Ricean fading affects the performance of STCs at finite SNR. We derive a code design criterion leading to robust STCs in a wide variety of propagation conditions and do not require any channel knowledge at the transmitter. Codes satisfying this criterion are shown to perform sensibly better in correlated channels than codes designed only for i.i.d. slow or fast Rayleigh-fading channels. Examples of space-time trellis codes and algebraic codes are proposed in order to illustrate the developed criterion.


Design sketching is an important and versatile skill for engineering students to master. Through it, students translate their design thoughts effectively onto a visual medium, whether to produce hand-drawn sketches onto paper, seamlessly interact with intelligent sketch-based modeling interfaces, or reap the advantages of educational benefits associated with drawing in general. Traditional instructional approaches for teaching design sketching are frequently constrained by the availability of experienced human instructors or the lack of supervised learning from self-practice, while relevant intelligent educational applications for sketch instruction have focused more on assessing users' art drawings or cognitive developmental progress. In this paper, we introduce an intelligent pen-based computing educational application that not only teaches engineering students how to hone and practice their design sketching skills through stylus-and-touchscreen interaction, but also aide their motivation and self-regulated learning through real-time feedback.


An application of cyber-physical testing to the empirical estimation of difference-frequency quadratic transfer functions is presented. As an alternative to today's procedure based on hydrodynamic tests with broad-banded or realistic (e.g., JONSWAP) wave spectra, tests in bichromatic waves are considered. The laboratory setup is the one developed by Sauder \& Tahchiev (2020) that enables magnifying the sensitivity of the floater response to the low-frequency wave loading by adjusting the stiffness and damping parameters of a virtual soft mooring system. Bayesian experimental design is proposed to optimize the selection of the control variables (frequencies in the bichromatic wave and properties of the virtual mooring system) for a batch of cyber-physical tests. The experimental design algorithm is based on the recent work of Huan \& Marzouk (2013). In a virtual yet realistic case study using an uncertain parametric quadratic transfer function, we demonstrate how the uncertainty of its describing parameters and other calibration parameters (low-frequency added mass and hydrodynamic damping) can be reduced. Results indicate that the proposed procedure has the potential for reducing experimental cost for calibration of hydrodynamic models.


Cloning systems like Gateway and Golden Gate/Braid are known because of their efficiency and accuracy. While the main drawback of Gateway is the expensive cost of the enzymes used in its two-step (LR and BP) reaction, Golden Gate requires non-reusable components due to their specific restriction sites. We present the Brick into the Gateway (BiG) protocol as a new cloning strategy, faster and more economic method that combines (i) reusable modules or bricks assembled by the GoldenBraid approach, and (ii) Gateway LR reactions [recombination of attachment sites: attL (L from left) and attR (R from right)] avoiding the BP reaction [recombination of attachment sites: attP (P from phage) and attB (B from bacteria)] usually necessary in the Gateway cloning. The starting point is to perform a PCR reaction to add type IIS restriction sites into DNA fragments generating specific fusion sites. Then, this PCR product is used to design GoldenBraid bricks, including the attL Gateway recombination sites. Using the Golden Gate method, these bricks are assembled to produce an attL1 -gene of interest- attL2 fragment, which is integrated into a compatible vector producing a Gateway entry vector. Finally, the fragment containing the target gene is recombined by LR reaction into the Gateway destination vector. This protocol was validated in: Plasmid (2022), DOI: 10.1016/j.plasmid.2022.102630 Graphical abstract.


Different crystalline phases (tetragonal zirconia, titanite, celsian, diopside, anortite, zircon, scheelite, casiterite, gahnite and spodumene) have been devitrificated into a transparent ceramic glaze by addition of oxides that acts as crystallisation agents. Microstructure, wear resistance and gloss of glass ceramic surface obtained on fired modified glazes are studied. All crystalline phases diminish the brittleness index of the original transparent glaze. Anortite stands out among reinforcing phases that produces dull surfaces associated with high roughness. On the other hand, zircon stands out among the phases that improve gloss surface together wear resistance.


OBJECTIVE
This exploratory study examined the ability of young adults to purchase alcoholic beverages through self-checkout lanes without being asked for age verification. Although the minimum drinking age in all 50 U. S. states is 21 years of age, drinking among underage persons (ages 12-20) remains a serious public health concern. Self-checkout options in off-sale alcoholic beverage outlets (e.g., grocery store chains, liquor stores) may represent a potential source of illicit access to alcohol compared with traditional checkout purchases.

METHOD
A total of 216 stores with self-checkout lanes were randomly selected in five Southern California counties. Pseudo-patrons independently judged to be 23 years of age or younger purchased alcohol in each store.

RESULTS
Overall, 8.8% of all purchase observations resulted in a failure to ask for identification to purchase alcohol.

CONCLUSIONS
The growing number of self-checkout options at supermarkets can be a potential source of alcohol for minors; however, the risk they pose is similar to that of traditional checkout purchases. Policies relating to the purchase of alcohol at any store, regardless of checkout type, should be modified so that every purchase of alcohol requires an identification card to be swiped regardless of age.


The equimolar reaction of calcium bis[bis(trimethylsilyl)amide] with 2,2,6,6-tetramethylheptane-3,5-dione (Htmhd) in THF yields liquid mononuclear [Ca(tmhd){N(SiMe3)2}(THF)3] (1). A similar reaction in toluene with a stoichiometric ratio of 2:3 gives the dinuclear complex [{(THF)Ca}2(tmhd)2(µ-tmhd){µ-N(SiMe3)2}] (2). The calcium atoms of these complexes are in a distorted octahedral environment. In 2 the complex consists of two octahedra connected by a common face of one nitrogen base and two oxygen atoms; the bridging Ca-N bond lengths are extremely large. The metalation of the tetradentate Jacobsen reagent with calcium bis[bis(trimethylsilyl)amide] in 1,2-dimethoxyethane (DME) gives the corresponding calcium complex 3, nearly quantitatively, as its DME adduct. The calcium atom is in an unusual trigonal prismatic coordination sphere. The metathesis reaction of 3 with tin(II) chloride yields the corresponding yellow tin(II) complex with the metal atom in a distorted square-pyramidal environment. Complexes 2 and 3 show catalytic reactivity in the ring-opening polymerization of cyclic esters such as lactones and lactides.


In model predictive control (MPC), the control input is computed by solving a constrained finite-time optimal control (CFTOC) problem at each sample in the control loop. The main computational effort when solving the CFTOC problem using an active-set (AS) method is often spent on computing the search directions, which in MPC corresponds to solving unconstrained finite-time optimal control (UFTOC) problems. This is commonly performed using Riccati recursions or generic sparsity exploiting algorithms. In this paper, the focus is efficient search direction computations for AS type methods. The system of equations to be solved at each AS iteration is changed only by a low-rank modification of the previous one, and exploiting this structured change is important for the performance of AS-type solvers. In this paper, theory for how to exploit these low-rank changes by modifying the Riccati factorization between AS iterations in a structured way is presented. A numerical evaluation of the proposed algorithm shows that the computation time can be significantly reduced by modifying, instead of re-computing, the Riccati factorization. This speedup can be important for AS-type solvers used for linear, nonlinear, and hybrid MPC.


Dissertation submitted for Partial Fulfillment of the Requirements for the Award of the Degree of MASTER OF SCIENCE
In Remote Sensing and Geographical Information Systems (GIS) Addis Ababa University, Addis Ababa, Ethiopia.


Over the last two decades, we have seen a radical change in therapy and progression of multiple myeloma, a malignant hematologic disease that is still considered fatal. Recent investment and research on mechanisms that interfere in the physiopathogenesis and bone marrow microenvironment are turning control and regression of the malignant plasma cell clone into something achievable, which may change expectations related to this disease. The new idea of using an old drug, thalidomide, has shown to be effective in multiple myeloma. In 1997, using the known effects of immunomodulation and antiangiogenesis of this drug, clinical trials were started in patients with unresponsive disease. Other therapeutic interventions in the bone marrow microenvironment and plasma cells have been added and proved to be efficacious, not only as a therapy for refractory patients, but also for induction and/or remission maintenance therapy. Thirty-five patients with multiple myeloma were treated with low-dose thalidomide (100 mg) and followed up. Thirteen were on maintenance therapy after bone marrow transplantation, eleven started thalidomide after induction therapy, five after relapse, four were refractory to usual therapies and two had induction therapy with thalidomide. The study took place in the Hematology and Bone Marrow Transplantation service of the Hospital de Clínicas de Porto Alegre, from March 2001 to December 2003. Hemoglobin levels, serum or urine immunoglobulin peaks and bone marrow plasma cell counts were evaluated. These parameters were assessed before starting with the drug and after 3.6 and 12 months of usage. The immunoglobulin level was considered the gold standard to evaluate the response. The results showed that 100 mg was the tolerable dose for 51% of the patients. Sixty-five percent of those who used thalidomide for induction therapy showed a 25 to 50% improvement in immunoglobulin serum levels and 90% of the patients on maintenance therapy (13 after bone marrow transplantation, 11 after induction), sustained the same immunoglobulin levels of the initial plateau. Rev. bras. hematol. hemoter. 2004;26(4):245-255.


Sepsis is a life-threatening clinical condition responsible for approximately 11 million deaths worldwide. Rapid and accurate identification of pathogenic bacteria and its antimicrobial susceptibility play a critical role in reducing the morbidity and mortality rates related to sepsis. Raman and infrared spectroscopies have great potential to be used as diagnostic tools for rapid and culture-free detection of bacterial infections. Despite numerous reports using both methods to analyse bacterial samples, there is to date no study collecting both Raman and infrared signatures from clinical samples simultaneously due to instrument incompatibilities. Here, we report for the first time the use of an emerging technology that provides infrared signatures via optical photothermal infrared (O-PTIR) spectroscopy and Raman spectra simultaneously. We use this approach to analyse 12 bacterial clinical isolates including six isolates of Gram-negative and six Gram-positive bacteria commonly associated with bloodstream infection in humans. To benchmark the single cell spectra obtained by O-PTIR spectroscopy, infrared signatures were also collected from bulk samples via both FTIR and O-PTIR spectroscopies. Our findings showed significant similarity and high reproducibility in the infrared signatures obtained by all three approaches, including similar discrimination patterns when subjected to clustering algorithms. Principal component analysis (PCA) showed that O-PTIR and Raman data acquired simultaneously from bulk bacterial isolates displayed different clustering patterns due to the ability of both methods to probe metabolites produced by bacteria. By contrast, signatures of microbial pigments were identified in Raman spectra, providing complementary and orthogonal information compared to infrared, which may be advantageous as it has been demonstrated that certain pigments play an important role in bacterial virulence. We found that infrared spectroscopy showed higher sensitivity than Raman for the analysis of individual cells. Despite the different patterns obtained by using Raman and infrared spectral data as input for clustering algorithms, our findings showed high data reproducibility in both approaches as the biological replicates from each bacterial strain clustered together. Overall, we show that Raman and infrared spectroscopy offer both advantages and disadvantages and, therefore, having both techniques combined in one single technology is a powerful tool with promising applications in clinical microbiology.


AIDS confronts the psychiatrist with the dilemma of stress resulting from a positive test result on the one hand and the responsibility of preventing the spread of the disease on the other hand. Psychiatric disturbances sometimes limit a patient's ability to give informed consent, which is an ethical precondition to testing. The legal standards of informed consent are discussed. During the 6-month period after the first HIV-positive test at Weskoppies Hospital, a further 48 patients were tested; 42 were examined to test the obtaining of informed consent. Diagnoses, reasons for testing and results were noted. Comprehension of the nature of the illness and the implications of the test were examined in a structured clinical interview. The nature of consent and the feedback of the result to the patient were examined. Results indicate that the psychiatric disturbance is a poor indication of the ability to give informed consent. The latter should be evaluated separately. If informed consent cannot be obtained, the patient should be treated as positive until accountability has been restored. Written consent offers the patient the opportunity to assimilate written information and contributes to informed consent. AIDS remains a problem of education and the feedback of seronegativity will help to curb future high-risk behaviour.


This thesis addresses the following research questions: 1. How is the process of corporate tax compliance changing for large groups of companies? 2. How is this process being managed by the Inland Revenue? The empirical evidence consists of 33 interviews conducted in 2002-04 with IR officials; tax directors and tax managers of large corporates; and tax partners from a Big 4 accounting firm. This· thesis also draws upon archival data including state papers and documentary data from the IR. Theoretically this thesis draws from the new public management, administration, and the tax compliance literatures. However I argue that an approach grounded purely i!1 these literatures does not adequately explain the changing tax compliance environment for large groups. Therefore I utilise other literatures which draw 'on Foucault's work on multiple expertise constructing subjects engaging with disciplinary knowledge and power, to assist in filling this gap. Against a backdrop where new organisational structures and processes are shifting a once bureaucratic Inland Revenue to a more strategic and marketing-based organisation, the corporate tax compliance process for large corporates has changed. Where the process was previously a long (in terms of time scale), formal and distant relationship with the IR carried out principally in writing, it has, while retaining aspects of this past, shifted towards being a mixture of the written and the oral, generating a more incll;lSive dialogue with the taxpayer, frequently in the form of meetings based on targeted yet potentially open-ended questioning. This has opened up what is described here as a new kind of 'truth game', which is less one based on inquisitorial practices but more based on examination techniques, played by knowledge experts: the IR official and the corporate taxpayer. Drawing on a governmentality framework as articulated by Foucault and his latter works, I argue that the nature of the corporate tax compliance game resembles a truth game between two kinds of subject generated in this transdisciplinary world: the new shape tax official and the visible customer (the taxpayer). The IR official - the lIM Inspector of Taxes, has been remoulded from one type of knowledge expert to another, which is a 3 dimensional transdisciplinary T shaped tax official. This is a tax official who both has the detailed deep technical knowledge as a knowledge expert but also has to relate, in a broader sense, to the new way of operating in a strategic and marketing organisation. The emergence of the corporate taxpayer as a visible customer has changed the process of corporate tax compliance for large corporates whereby they exercise certain power in the relationship by virtue ofthis visibility. This research tracks a new kind of interaction of the interplay between subjectivization and objectivization which seems to have become established and develops a theoretically informed way of looking at emergent governmental and more wide ranging forms of application.


The literature on the molecular genetic mechanisms for antigenic variability of pathogenic bacteria is reviewed. Ability to antigenic variability in any case discussed is considered to be a pathogenicity factor permitting efficient struggle against the immune system of the host-organism. The molecular basis for such variability is instability of the genome structure, coding for highly immunogenic bacterial proteins.


In this paper we study the transient surface cavity which is created by the controlled impact of a disk of radius h0 on a water surface at Froude numbers below 200. The dynamics of the transient free surface is recorded by high-speed imaging and compared to boundary integral simulations giving excellent agreement. The flow surrounding the cavity is measured with high-speed particle image velocimetry and is found to also agree perfectly with the flow field obtained from the simulations. We present a simple model for the radial dynamics of the cavity based on the collapse of an infinite cylinder. This model accounts for the observed asymmetry of the radial dynamics between the expansion and the contraction phases of the cavity. It reproduces the scaling of the closure depth and total depth of the cavity which are both found to scale roughly as ∝ Fr1/2 with a weakly Froude-number-dependent prefactor. In addition, the model accurately captures the dynamics of the minimal radius of the cavity and the scaling of the volume Vbubble of air entrained by the process, namely, Vbubble/h03∝(1 + 0.26Fr1/2)Fr1/2.


Cervical spondylotic myelopathy is a well-known cause of disability among older people. A significant amount of these patients is asymptomatic. Once the symptoms start, the worsening may follow a progressive manner. We should suspect of spondylotic myelopathy in any individual over 55 years presenting progressive changes in gait or losing fine motor control of the upper limbs. Despite its frequent prevalence, this condition is still neglected and many times confused with other supratentorial lesions regarding diagnostic. Here we address some of most important aspects of this disease, calling attention to pathophysiology, the natural history, presentation, differential diagnosis, clinical assessment, and treatment.


Functional Characterization of the Mammalian TRPV4 Channel: Yeast Screen Reveals Gain-of-Function Mutations Christina A. Doyle Transient receptor potential (TRP) channels are a class of six-transmembrane (6-TM) cation-permeable channels that mediate flux of calcium and sodium into cells, leading to depolarization as well as activation of calcium-mediated second-messenger signaling pathways. The TRP channel family is large and diverse in terms of tissue expression, mechanism, and function; therefore, sub-classification is primarily through amino acid homology. A general role has emerged for TRP channels, though, in the processing of sensory stimuli at both the cellular and organismal level. The goal of this study was to perform mutagenesis screens of mammalian TRP channels to reveal key structural determinants of channel activity (such as gating, permeation, and selectivity). We screened for gain-of-function alleles of TRP channels by their ability to rescue growth deficiency of a strain of the yeast Saccharomyces cerevisiae caused by lack of ion efflux. Channels were further characterized through electrophysiological analysis of their activity when heterologously expressed in Xenopus laevis oocytes. Of the subset of mammalian TRP channels tested, only wild type TRPV4 rescued the ability of the yeast strain trk1Δ trk2Δ to grow on low potassium media. The TRPV4 channel is important in thermosensitive, osmosensitive, and mechanosensitive processes; recently, mutations of TRPV4 have been linked to human skeletal and neurodegenerative disorders. We obtained a loss-of-function variant of TRPV4 containing the substitutions K70E (N-terminal tail) and M605T (intracellular linker between transmembrane helices S4 and S5) that failed to rescue low potassium growth of trk1Δ trk2Δ. Therefore, we screened for compensatory mutations that would restore the ability of the V4-K70E/M605T channel to rescue the yeast growth phenotype. Five gain-of-function clones were isolated, containing a total of seven mutations: three substitutions in the N-terminal tail (R151W, P152S, L154F), one substitution in the pore-lining S5 transmembrane helix (M625I), one substitution in the C-terminal tail (H787Y), and two truncations of the C-terminal tail (N789Δ and Q790Δ). Each of these mutations was assayed, in both the variant V4-K70E/M605T and the wild type TRPV4 background, for effect on rescue of trk1Δ trk2Δ yeast low-potassium growth, as well as degree of salt sensitivity conferred on wild type yeast. We also performed two-electrode voltage-clamp (TEVC) recordings of the mutant channels expressed in Xenopus oocytes, obtaining preliminary data on the ability of the mutations to restore a calcium-activated sodium current to V4-K70E/M605T that was present in wild type TRPV4. Given the known importance of the S5 helix in gating, the mutation M625I most likely has an effect on gating of the intracellular pore. This mutation showed strong rescue of low potassium growth and salt sensitivity in yeast, and preliminary data showed strong rescue of calcium-activated current in oocytes. An autoinhibitory channel structure is formed by binding of the C-terminal calmodulinbinding domain to a portion of the N-terminus, which is disrupted by the binding of calciumcalmodulin to the C-terminal domain. The point mutations we isolated in the Nand C-termini lie just outside these respective regions, leading us to believe that the gain-of-function phenotype could be due to disruption of this autoinhibitory structure. Although the C-terminal truncations were isolated with a gain-of-function phenotype in V4-K70E/M605T (rescue of low-potassium yeast growth), introduction of the truncations into wild type TRPV4 led to a loss-of-function phenotype: truncated channels no longer induced yeast salt sensitivity and exhibited no calcium-activated current in oocytes. This phenotype could be due to the loss of the calmodulin-binding domain, suggesting that the potentiation of channel activity by calcium involves mechanisms other than simply the disruption of the autoinhibitory domain. However, it is also possible that the phenotype is merely the result of reduced membrane expression: some studies indicate that truncation of the C-terminal tail leads to ER retention of the protein. Taken together, the results of our three assays provide insight into the mechanisms of TRP channel function. Combined with what is already known about these channel regions, we are able to draw conclusions as to the potential contribution of these residues on channel activity and add to the body of evidence regarding mechanisms of function of the TRPV4 channel.


Objective Accurately predicting the prognosis of young patients with breast cancer (<40 years) is uncertain since the literature suggests they have a higher mortality and that age is an independent risk factor. In this cohort study we considered two prognostic tools; Nottingham Prognostic Index and Adjuvant Online (Adjuvant!), in a group of young patients, comparing their predicted prognosis with their actual survival. Setting North East England Participants Data was prospectively collected from the breast unit at a Hospital in Grimsby between January 1998 and December 2007. A cohort of 102 young patients with primary breast cancer was identified and actual survival data was recorded. The Nottingham Prognostic Index and Adjuvant! scores were calculated and used to estimate 10-year survival probabilities. Pearson's correlation coefficient was used to demonstrate the association between the Nottingham Prognostic Index and Adjuvant! scores. A constant yearly hazard rate was assumed to generate 10-year cumulative survival curves using the Nottingham Prognostic Index and Adjuvant! predictions. Results Actual 10-year survival for the 92 patients who underwent potentially curative surgery for invasive cancer was 77.2% (CI 68.6% to 85.8%). There was no significant difference between the actual survival and the Nottingham Prognostic Index and Adjuvant! 10-year estimated survival, which was 77.3% (CI 74.4% to 80.2%) and 82.1% (CI 79.1% to 85.1%), respectively. The Nottingham Prognostic Index and Adjuvant! results demonstrated strong correlation and both predicted cumulative survival curves accurately reflected the actual survival in young patients. Conclusions The Nottingham Prognostic Index and Adjuvant! are widely used to predict survival in patients with breast cancer. In this study no statistically significant difference was shown between the predicted prognosis and actual survival of a group of young patients with breast cancer.


Abstract Effects of microgravity (μG) on fertilization were studied in the urodele amphibian Pleurodeles waltl on board the MIR space station. Genetic and cytomorphologic analyses ruled out parthenogenesis or gynogenesis and proved that fertilization did occur in μG. Actual fertilization was demonstrated by the analysis of the distribution of peptidase-1 genes, a polymorphic sex-linked enzyme, in progenies obtained in μG. Further evidence of fertilization was provided by the presence of spermatozoa in the perivitelline space and in the fertilization layer of the μG eggs and by the presence of a female pronucleus and male pronuclei in the egg cytoplasm. Experiments in μG and in 1.4G, 2G, and 3G hypergravity showed for the first time that, compared to eggs in 1G, several characteristics of the fertilization process including the cortical reaction and the microvillus transformations were altered depending on the gravitational force applied to the eggs. Microvillus elevation, the most evident feature, was reduced on μG-eggs and amplified on eggs submitted to 2G and 3G. No lethal consequences of these alterations on the early development of μG-eggs were observed.


Summary It may be possible to identify elements of psychosomatic/psychotherapeutic primary care in the Federal Republic of Germany and the former German Democratic Republic by comparing the current state of basic psychosomatic care (BPSC) in the eastern and western part of Berlin. 278 Berlin patients with psychosocial problems were recruited 1995 for a basic documentation system of the BPSC in connection with a project supported by the Federal Ministry for Health at the Berlin Center. Their data were compared with regard to diagnostic and therapeutic measures applied in the eastern and western part of Berlin. Furthermore, 617 questionnaires on basic psychosomatic care were filled out by physicians in private practice in both parts of the city in 1994. Despite the identical or lower assessment of their patients* biopsychosocial stress, East Berlin physicians take considerably more therapeutic measures than their colleagues in West Berlin. There are only minor differences between physicians from the east...


Purpose Chronic hepatitis C virus (HCV) infection is an important public health concern. Limited information exists on disparities in the quality of HCV care. We examine disparities in genotype or quantitative HCV ribonucleic acid testing before and after starting HCV treatment, and screening for hepatocellular carcinoma (HCC) in HCV patients with cirrhosis. Methods This national study included Medicare beneficiaries with HCV between 2014 and 2017. We used bivariate probit to estimate the probability of receiving recommended tests before and after HCV treatment by patient race/ethnicity, urban/rural residence, and socioeconomic status. We used multivariate logistic regression to estimate adjusted odds ratios (aOR) of HCC screening among beneficiaries with cirrhosis by patient factors. Findings Of 41,800 Medicare patients with HCV treatment, 93.47% and 84.99% received pre- and post-treatment testing. Patients in racial minority groups had lower probabilities of pre- and post-treatment testing than whites. Rural residents were less likely to receive a post-treatment test (Coef. = -0.06, 95% CI: -0.11, -0.01). Among HCV patients with cirrhosis, 40% (24,021) received at least one semi-annual HCC screening during the study period. The odds of HCC screening were 14% lower in rural than in urban patients (aOR = 0.86, 95% CI: 0.80, 0.92), lower in African Americans (aOR = 0.93, 95% CI: 0.90, 0.96), but higher among Hispanics than in whites (aOR = 1.09, 95% CI: 1.04, 1.15). There was no significant association between ZIP-level income or education and HCC screening. Conclusions Disparities in the quality of HCV care existed by patient race/ethnicity, urban/rural residence, and socioeconomic status. Continued efforts are needed to improve the quality of care for all HCV patients—especially rural patients and racial/ethnic minorities.


Magma plumbing systems represent the physical framework of magma transport and storage from the source region in the mantle, through the crust, until reaching the surface in a volcanic eruption. Characterising the different aspects of magma plumbing, in particular the distribution of magma storage zones throughout the crust, is of key importance to better understand the behaviour of individual volcanoes. In particular, shallow crustal magma storage and associated magma-crust interaction processes could potentially explain some of the worlds most unpredictable and explosive volcanoes. This thesis studies magma plumbing architecture in the Sunda Arc (Indonesia), and the North Atlantic Igneous Province, based on elemental and isotope geochemistry, and derived petrological modelling.In this study, I have employed petrological models, so called geothermobarometers, to calculate pressures and temperatures (P-T) of crustal magma storage. Geothermobarometers are calibrated thermodynamic formulations based on the composition of magmatic minerals and their co-existing melt as a function of the P-T conditions of crystallisation. Using the calculated P-T estimates, I was able to derive the depth of magma storage, and thereby reconstruct the architecture of magma storage systems. A number of different geothermobarometers based on different mineral phases, including plagioclase, clinopyroxene and olivine, were used for this purpose,The geothermobarometric modelling was combined with additional elemental and isotope geochemical analyses, as well as collaborations with geophysical investigations. These additional approaches were used to corroborate the findings of the geothermobarometric modelling, and also to model and quantify magma-crust interaction processes that take place during crustal magma storage, such as assimilation of crustal lithologies into the magmatic system.The findings of this thesis build upon the growing body of evidence in support of the prevalence of shallow magma storage in different volcanic settings worldwide. This realisation is relevant to volcano monitoring and hazard mitigation worldwide.


In this article, we introduce a novel group of space-time-frequency codes based on multiple trellis coded modulation (MTCM). These codes are originally designed without accounting for the channel spectral and temporal correlation conditions. We improve the code performance by utilizing an augmented distance spectrum enhancement technique to serve for the wireless channels that undergo mobility and multi path fading. The performance of the new group of codes, with enhanced distance spectrum characteristics is investigated though numerical simulations


The requirement for on-line and in-situ monitoring of analytes in process and effluent streams and in ground waters has become increasingly more important in recent years. We therefore describe the development of the transduction element for a fully automated online instrument for the detection of caesium. The sensor layer for this instrument employs an Ion Selective Conductimetric Microsensor (ISCOM) as the detector. This is based upon a plasticized polymeric membrane incorporating a selective ionophore, overlaying two interdigitated microelectrode arrays. A direct relationship has been observed between the bulk conductance (as determined by the microelectrodes) of the ionophore loaded membrane and the concentration of the primary ions in solution. Caesium selective ISCOMs were prepared using an ion selective membrane containing the commercially available ionophore Calix [6]arene-hexaacetic acid hexaethyl ester, polyvinylchloride (PVC) and plasticiser Nitrophenylether (NPOE). The relative levels of membrane components have also been varied in order to further enhance the ISCOM response. We also present preliminary data concerning the caesium selectivity with respect to a range of possible interferents, including rubidium.


Fixed drug eruptions (FDE) are the common dermatological adverse drug reaction accounts for 16–21% of all cutaneous drug reactions in India. Drugs most frequently implicated in FDE are antimicrobials, anticonvulsants, and nonsteroidal antiinflammatory drugs. Here, we report a rare case of bullous FDE due to ciprofloxacin followed by ofloxacin administration.


What is it that helps printed newspapers successfully compete with other media for the audience — their marketing efforts, the content they offer, or their design? This paper summarizes the results of an extensive research program, the evaluation of 350 typical local dailies in Germany. They were analyzed thoroughly in 1989 and again in 1994. In addition, a survey provided extensive information about their marketing measures during that period. Finally, socio-demo-graphic and other conditions that newspapers are confronted with in their trade areas were included in the analysis. Criteria for success were the circulation and the reach of every newspaper. Newspaper design, in general, proved to be a little more important than content and marketing for attracting new readers and for keeping old ones. Different strategies, though, seem to apply depending on whether a newspaper wants to reach young or less educated readers or has to compete with other local papers. In general, however, an 'airy,' well-structured design, a greater variety of topics every day, more local orientation and the strict separation of news and entertainment were the best recipes for newspaper success.


This work aimed to describe the skeletopy of the medullary cone of the capuchin monkey (Sapajus apella) and to lay morphological foundations to propose a route of administration for epidural anesthesia. We used five females adults S. apella, and dissected them to study their medullary cone. The fixated animals were dissected, a skin incision was made from the dorsal median line, epaxial musculature and vertebral arcs was removed to expose the spinal cord, individualizing the medullary cone and the lumbar intumescence. The base of S. apella medullary cone was located near the L5 vertebra and the apex near S3, the structure was 4.5 cm in average. The evaluated specimens presented five lumbar and four sacral vertebrae. We concluded that the positioning of S. apella medullary cone is caudally than in other species, suggesting that the most appropriate location for epidural anesthetic procedures is the sacrocaudal region.


What new challenges does the combination of games and eye-tracking present? The EyePlay workshop brings together researchers and industry specialists from the fields of eye-tracking and games to address this question. Eye-tracking been investigated extensively in a variety of domains in human-computer Interaction, but little attention has been given to its application for gaming. As eye-tracking technology is now an affordable commodity, its appeal as a sensing technology for games is set to become the driving force for novel methods of player-computer interaction and games evaluation. This workshop presents a forum for eye-based gaming research, with a focus on identifying the opportunities that eye-tracking brings to games design and research, on plotting the landscape of the work in this area, and on formalising a research agenda for EyePlay as a field. Possible topics are, but not limited to, novel interaction techniques and game mechanics, usability and evaluation, accessibility, learning, and serious games contexts.


Balancing concise mathematical analysis with the real-world examples and practical applications that inspire students, this textbook provides a clear and approachable introduction to the physics of waves. The author shows through a broad approach how wave phenomena can be observed in a variety of physical situations and explains how their characteristics are linked to specific physical rules, from Maxwell's equations to Newton's laws of motion. Building on the logic and simple physics behind each phenomenon, the book draws on everyday, practical applications of wave phenomena, ranging from electromagnetism to oceanography, helping to engage students and connect core theory with practice. Mathematical derivations are kept brief and textual commentary provides a non-mathematical perspective. Optional sections provide more examples along with higher-level analyses and discussion. This textbook introduces the physics of wave phenomena in a refreshingly approachable way, making it ideal for first- and second-year undergraduate students in the physical sciences.


Streptococcus mutans is important in dental caries. Although the role of cytokines in the pathogenesis of dental caries is not clear, components of S. mutans were found to stimulate production of pro-inflammatory cytokines. We examined the associations of interleukin (IL)-1β, IL-1 receptor antagonist (IL-1ra), and IL-10 with dental caries. Unstimulated whole saliva and blood samples were obtained from 108 children aged 6-12 years with high caries (decayed, missing, or filled teeth [dmft/DMFT] index >4, n = 37), moderate caries (dmft/DMFT = 1-4, n = 37), or caries-free (dmft/DMFT = 0, n = 34). S. mutans level was classified as low (<10(5) colony-forming units [CFU]/mL) or high (≥10(5) CFU/mL). Saliva and serum concentrations of IL-1β, IL-1ra, and IL-10 were determined by ELISA. IL-1β, IL-1ra, and IL-10 gene polymorphisms were genotyped using PCR and restriction fragment length polymorphism analysis. The chi-square, Mann-Whitney U, one-way ANOVA, posthoc, Fisher's exact, and t tests were used in statistical analysis. Dental caries was not correlated with salivary or serum concentrations of the studied cytokines. S. mutans level positively correlated with saliva IL-1β concentration and inversely correlated with saliva IL-1ra concentration. There was no correlation of IL-1β, IL-1ra, or IL-10 gene polymorphisms with dental caries. S. mutans is important in stimulating saliva IL-1β and inhibiting IL-1ra. Future studies of associations between cytokines and dental caries should investigate additional cytokines and enroll a larger number of participants.


A thorough history and physical examination con establish the diagnosis of tension headache; further evaluation is generally unnecessary. In contrast, the workup of cervicogenic headache includes standard radiographs, 3-dimensional CT, MRI, and possibly electromyography; nerve blocks may also be used to confirm the diagnosis. Episodic tension headache can be treated effectively by trigger avoidance, behavioral modulities, and structured use of analgesics. Reserve opioids for patients with intructuble headuches. Chronic tension headache is treated primarily by prophylactic measures, such as antidepressants and anticonvulsonts, and behavioral and physical therapy. Treatment options for cervicogenic headuche include analgesics; invasive procedures, such as trigger point injections, greater or lesser occipital nerve blocks, facet joint blocks, segmental nerve root blocks, and diskography; spinal manipulation; and behavioral approaches.


A publication in two parts: one a hard-bound book that includes the script for 'At Twilight: A play for two actors, three musicians, one dancer, eight masks (and a donkey costume)' by Graham Eatough and Simon Starling, first performed in Glasgow in 2016; and the other a tabloid-format newspaper that documents the exhibition 'At Twilight' and the live performances at Hollywood House, Glasgow. The publication includes texts by Katrina Brown, Director of The Common Guild, and Yukie Kamiya, Director of The Japan Society Gallery, alongside character biographies written by Simon Starling and source material selected by the artist. Designed by graphic design collective Abake to accompany the exhibitions 'At Twilight' at The Common Guild 2 July – 4 September 2016 and 'At Twilight (After W.B. Yeats' Noh Reincarnation)' at Japan Society, New York 14 October 2016 – 15 January 2017.


The effect of a single injection of live M. arthritidis microorganisms on the bone marrow and spleen CFU-S populations was assessed. One of the principal findings is that marrow CFU-S are recruited into cell cycle (as determined by hydroxyurea kill) early after M. arthritidis administration and stay in the cycle for at least 2 weeks thereafter. The peak level of cycling value (47%) was observed on day 4. The duration of increased CFU-S cycling activity was shown to coincide with a time period during which a significant rise in the number of endogenous CFU-S was maintained. The other important finding is that splenic seeding efficiency ("f-factor") declines by 56% one day following M. arthritidis administration. The latter effect could be attributed to the binding of mycoplasmas to the surface of CFU-S as specific rabbit antiserum against M. arthritidis incubated in vitro with the bone marrow cells of infected donor mice caused an up to 48% reduction in the in vivo colony-forming ability of CFU-S.


Diet of the spotted spiny dogfish, Squalus suckleyi, in Marmot Bay, Gulf of Alaska was studied from small-mesh surveys and large-mesh surveys conducted by Alaska Department of Fish and Game and the National Marine Fisheries Service between 2006 and 2014. A total of 333 spotted spiny dogfish stomachs were analyzed. By weight, the diet consisted mainly of Teleostei, and Cephalopoda. A total of 13 species of Teleostei were identified. The most frequently occurring fish taxa were walleye pollock (Gadus chalcogramma), capelin (Mallotus villosus), Pacific herring (Clupea pallasi), and eulachon (Thaleichthys pacificus). Euphausiids and pandalid shrimp were the most frequently occurring invertebrates.


Purpose This study was meant to analyze immune infiltration and construct a ceRNA network to explore the new therapeutic targets for atopic dermatitis (AD) through bioinformatics way. Patients and Methods We downloaded the AD patients' RNA expression profile datasets (GSE63741, GSE124700) from the Gene Expression Omnibus (GEO) database, which were analyzed through the GEO2R. We explored the hub genes by the enrichment analysis and the protein–protein interaction (PPI) analysis. Moreover, we estimated immune cell types and their proportions by ImmucellAI. GSE121212 dataset validation was performed to verify the robustness of the hub genes. Then, a ceRNA network was constructed by the miRWalk, miRNet, miRDB, DIANA, TargetScan, and starbase database. Finally, gene expression analysis was performed by using RT-qPCR. Results In total, we detected 22 differentially expressed genes (DEGs), which contained 8 downregulated genes and 14 upregulated genes. There were 5 hub genes confirmed as key genes through PPI network analysis and the ROC curves. KEGG pathway analysis revealed that they were significantly enriched in the IL-17 signaling pathway and GO analysis showed mainly in the immune cell chemotaxis. The immune infiltration profiles were different between normal controls and AD, and each of the key genes (S100A7, S100A8, S100A9, and LCE3D) was significantly correlated with the main infiltration cell of AD. A lncRNA–miRNA–mRNA ceRNA network containing the key genes was constructed, and NEAT1 and XIST, the core of ceRNA network, were significantly overexpressing verified by RT-qPCR in AD patients. Conclusion Altogether, the key genes and their ceRNA network provided a novel perspective to the immunomodulation of AD, which may be potential and new therapeutic targets for AD.


The WHO recommendations for hospital cancer registration, although being effective for combating the disease, need heavy manpower for complete implementation. A computer-based method for cancer registration is in use at Kyushu University Hospital as part of the integrated hospital information system. This method needs no manpower for data gathering, and the database includes almost all the core data and half of optional data recommended for cancer registration by the WHO. This database can, therefore, be regarded as a file for hospital cancer registration, and is used for two applications. The prepared form is automatically completed for the regional cancer register by a computer program without involving any physicians' time. In addition, a decision support system for the protocol used for a patient \\it11 ii cancer \YBS developed. Trend tables and graphs of clinical examinations and medication are displayed, with suggestions and \varnings for physicians to help them make clinical decisions.


Due to rapid technology advance, multiprocessor system-on-chips (MPSoCs) are likely to become commodity computing platforms for embedded applications. In the future, it is possible that an MPSoC is equipped with a large number of processing elements as well as on-chip resources. The management of these faces many challenges, among which deadlock is one of the most crucial issues. This paper presents a novel hardware-oriented deadlock detection algorithm suitable for current and future MPSoCs. Unlike previously published methods whose runtime complexities are often affected by the number of processing elements and resources in the system, the proposed algorithm leverages specialized hardware to guarantee O(1) overall runtime complexity. Such complexity is achieved by: 1) classifying resource allocation events; 2) for each type of events, using hardware to perform a set of specific detection and/or preparation operations that only takes constant runtime; and 3) updating necessary information for multiple resources in parallel in hardware. We implement the algorithm in Verilog HDL and demonstrate through simulation that each algorithm invocation takes at most four clock cycles.


In order to properly identify and treat those children with visually related reading problems, a diagnostic flow chart was developed to assist optometrists with this task. This diagnostic tool addresses ten of the most commonly encountered visual problems associated with reading. It is a "user friendly" product that easily moves between some of the common signs/symptoms presented by your patients and an appropriate diagnostic condition. Within each diagnostic condition are the following sections: a short description, other signs and symptoms, and suggested treatment options for this condition. This diagnostic flow chart and CD are included in the appendix section of this document and is available for anyone's use. Our hope is that optometrists will find this product useful and therefore, children with visually related reading problems will receive the proper treatment so that they can reach their full potential.


Regulatory T cells (Tregs) are a distinct lymphocyte lineage, functionally defined as T cells that inhibit an immune response, which is crucial for maintaining peripheral tolerance and the prevention of autoimmunity. Tregs have been implicated in tumour immune evasion, suppressing the anti-tumour immune response, resulting in tumour progression. The aim of this PhD was to recognise how Tregs function and understand how they are able to modulate tumour immunology. In order to research their proposed role in cancer, it was necessary to be able to phenotype, sort and expand functional Tregs. In preliminary research, strategies were designed to phenotype and test the functionality of ex vivo Tregs and commercial isolation kits were tested and compared in terms of cost efficiency and effectiveness. The mechanisms of Treg-mediated suppression were investigated, including the necessity for cell-to-cell contact and the involvement of key cytokines. The importance of particular cytokines in Treg-mediated suppression was not clear; but cell contact appears to be required for optimal suppression.

The project then aimed to address whether or not the importance of Tregs highlighted in the literature was reflected in a clinical setting. The significance of immune cell orientation within the tumour microenvironment was researched, investigating the co- localisation between key immune cell subtypes and their correlation with areas of tumour proliferation, apoptosis, hypoxia and vasculature coverage. In order to achieve this successfully, immunohistochemical techniques were optimised and image analysis algorithms were constructed to facilitate rigorous and systematic quantification of immune cell infiltrates in primary colorectal and metastatic liver cancer patients. Significant increases in the prevalence of Tregs, CD8 cells, macrophages and natural killer (NK) cells were observed within the stroma, compared with the tumour. A metastatic phenotype was alluded to; encompassing elevated Tregs and reduced numbers of CD8 cells.

Further to this, the level of Tregs in the peripheral blood and tumour tissue of liver- metastatic patients were assessed to investigate whether any correlation existed between circulating and tumour-infiltrating Tregs. It was shown that within peripheral blood, patients exhibited a TreghighCD8lowNKlow phenotype, when compared with healthy volunteers.

Finally, the project aimed to build an in vitro human Treg tumour-killing suppression model to examine the ability of Tregs to inhibit NK cell-mediated cytotoxicity. The mechanism for this was investigated, evaluating the importance of the NK group 2 member D (NKG2D) receptor ligand interaction, to mediate cell killing in a transforming growth factor-β dependent manner.

This study adds to the ongoing discussion on the role of immune cells in metastatic development. Accumulating evidence points to a critical role of immune infiltrates in allowing metastatic development, where Tregs support tumour growth by suppressing the host anti-tumour immune response.


Lactoferrin (LF) is a mammalian host defense glycoprotein with diverse biological activities. Peptides derived from the cationic region of LF possess cytotoxic activity against cancer cells in vitro and in vivo. Bovine lactoferricin (LFcinB), a peptide derived from bovine LF (bLF), exhibits broad-spectrum anticancer activity, while a similar peptide derived from human LF (hLF) is not as active. In this work, several peptides derived from the N-terminal regions of bLF and hLF were studied for their anticancer activities against leukemia and breast-cancer cells, as well as normal peripheral blood mononuclear cells. The cyclized LFcinB-CLICK peptide, which possesses a stable triazole linkage, showed improved anticancer activity, while short peptides hLF11 and bLF10 were not cytotoxic to cancer cells. Interestingly, hLF11 can act as a cell-penetrating peptide; when combined with the antimicrobial core sequence of LFcinB (RRWQWR) through either a Pro or Gly-Gly linker, toxicity to Jurkat cells increased. Together, our work extends the library of LF-derived peptides tested for anticancer activity, and identified new chimeric peptides with high cytotoxicity towards cancerous cells. Additionally, these results support the notion that short cell-penetrating peptides and antimicrobial peptides can be combined to create new adducts with increased potency.


This position paper describes the Activity-Based Computing (ABC) project which has been ongoing in Denmark since 2003. Originally, the project took its outset in the design of a pervasive computing platform suited for the mobile, collaborative, and time-critical work of clinicians in a hospital setting. Out of this grew a conceptual framework, a set of six ABC principles, and a programming and runtime framework for the development of activity-based computing infrastructures and applications. Lately, these principles and technologies have been successfully moved to other application areas, and is now used to design and implement activity-based computing support for work in a biology laboratory and for global software development.


Type 2 diabetes is becoming a major cause of chronic renal failure leading to health care problem. Literature data do not allow to choose between hemodialysis or peritoneal dialysis as the treatment of choice of end stage renal failure in type II diabetic patients according to their co-morbidities. A retrospective study was performed in 28 type II diabetic patients, either 11% of the total population, who started dialysis in our center between 1994 and 1997. Fourteen patients had chosen peritoneal dialysis and 14 hemodialysis. The 2 groups were not different for their initial neurological, cardiovascular, ophthalmological complications and for their metabolic control. After a mean follow-up of 14 months on dialysis a significant higher number of infections (9 versus 4), of hospitalisation days (34 +/- 19 versus 6.5 +/- 5.5), of technical transfers (6 versus 0) and of deaths (5 versus 0) were recorded in patients on peritoneal dialysis, without any difference in the metabolic control. A prospective, multicenter study is required to identify the best dialysis technique in type 2 diabetic patients, according to their co-morbidities and the dialysis dose.


The internet has proved to be one of the greatest learning resources available in the 21st Century. Modern education is becoming progressively more dynamic. Internet has helped man to see the other part of the world at the click of a mouse. Various forms of instructional technologies such as the overhead projector, opaque projector, filmstrip and slide projectors, radio and television to mention but a few have been used as media in instructional process. In recent times, e-learning emerged as the fastest means by which one can teach and learn online. This paper explores the concept of e-learning. It outlined and discussed the needed e-learning resources for the usage of academic adult educators. Some of them are Computer, CD-ROM Packages, videophone system and digital library. It enumerated the benefits of e-learning to academic adult educators such as collaborative studies, virtual library. It recommends among other things that the government of Nigeria should provide computerized/digital libraries for accessibility of information in the internet.