To assess the role of brain antioxidant capacity in the pathogenesis of neonatal hypoxic-ischemic brain injury, we measured the activity of glutathione peroxidase (GPX) in both human-superoxide dismutase-1 (hSOD1) and human-GPX1 overexpressing transgenic (Tg) mice after neonatal hypoxia-ischemia (HI). We have previously shown that mice that overexpress the hSOD1 gene are more injured than their wild-type (WT) littermates after HI, and that H2O2 accumulates in HI hSOD1-Tg hippocampus. We hypothesized that lower GPX activity is responsible for the accumulation of H2O2. Therefore, increasing the activity of this enzyme through gene manipulation should be protective. We show that brains of hGPX1-Tg mice, in contrast to those of hSOD-Tg, have less injury after HI than WT littermates: hGPX1-Tg, median injury score = 8 (range, 0–24) versus WT, median injury score = 17 (range, 2–24), p < 0.01. GPX activity in hSOD1-Tg mice, 2 h and 24 h after HI, showed a delayed and bilateral decline in the cortex 24 h after HI (36.0 ± 1.2 U/mg in naive hSOD1-Tg versus 29.1 ± 1.7 U/mg in HI cortex and 29.2 ± 2.0 for hypoxic cortex, p < 0.006). On the other hand, GPX activity in hGPX1-Tg after HI showed a significant increase by 24 h in the cortex ipsilateral to the injury (48.5 ± 5.2 U/mg, compared with 37.2 ± 1.5 U/mg in naive hGPX1-Tg cortex, p < 0.008). These findings support the hypothesis that the immature brain has limited GPX activity and is more susceptible to oxidative damage and may explain the paradoxical effect seen in ischemic neonatal brain when SOD1 is overexpressed.


Aims: This study assessed the morphology and the bait preference of black rat (Rattus rattus) in Obafemi Awolowo University student hostel with the aim of controlling the population of black rat in the students' hostels.
Place and Duration of the Study: The study was carried out at Obafemi Awolowo University which is situated in Ile-Ife, an ancient city in the Southwestern Nigeria and lies between latitudes 7°28′N and 7.467°N and longitudes 4°34′E and 4.567°Ewith a landmass of 5,506 hectares between December 2017 and February 2018
Methodology: Locally made metal traps (cage traps) (Plate 1) contains baits were placed fortnightly in various sampling locations (Awolowo, Fajuyi, Angola, Akintola, Mozambique and Moremi halls of residence) for a period of 3 months between the months of December 2017 to February 2018. The traps were set around the dark corners of the sites in the evening and collected the following morning (6.00am).
Results: A total of 236 black rats (Rattus rattus) were caught (81 male & 155 female), with the female having the highest weight (238.30 g). Among the baits used, fried fish caught the highest number of the black rat (58%) followed by beans cake (akara) (28%) and the locust bean (14%). There was a positive correlation in the morphology of the black rat caught in all the hostels.
Conclusion: The black rats in the University student hall of residence were of the same family and genus, and fried fish is the best-preferred bait.


Objective: We investigated the presence of both hypertension and diabetes mellitus in two management settings, namely cardiology and endocrinology, and its association with albuminuria while accounting for the management of these two diseases. Design and Method: Our multicentre registry included patients (≥ 20 years) seen for hypertension in cardiology or for diabetes mellitus in endocrinology. We administered a questionnaire and measured blood pressure, glycosylated haemoglobin A1c (HbA1c) and albuminuria. Results: The presence of both hypertension and diabetes was observed in 32.9% of hypertensive patients in cardiology (n = 1291) and 58.9% of diabetic patients in endocrinology (n = 1168). Presence of both diseases was associated with a significantly (P ⩽ 0.01) higher use of combination antihypertensive therapy in cardiology (odds ratio 1.36). The control of hypertension and diabetes was not different between patients with both diseases and those with either condition alone (P≥0.08), regardless of the therapeutic target (systolic/diastolic blood pressure < 140/90 or 130/80 mmHg and HbA1c <7.0% or 6.5%) or management setting. The prevalence of albuminuria, however, was higher (P ⩽ 0.02) in the presence of both diseases (23.3%) than those with either hypertension (12.6%) or diabetes alone (15.9%), especially in uncontrolled hypertension (systolic/diastolic pressure ≥140/90 mmHg), which was associated with a higher risk of albuminuria in the presence (odds ratio 2.48, P = 0.004) but not absence of diabetes (P = 0.17). Conclusions: The presence of both hypertension and diabetes mellitus was prevalent, especially in the endocrinology setting. It was associated with higher risk of target organ damage, and required more intensive management and better control of both conditions, particularly hypertension.


People with Down syndrome suffer from many social, psychological and motor function problems. Current research has looked at swimming programmes to assess their impact on such problems. The programme described here was applied for a 3-month period, with music being used as one of the tools. The results were very positive and children showed significant improvement in agility, self-esteem and behaviour patterns. The programme is thus effective in enhancing the integrated development of children with Down syndrome.


The myoelectric activity of agonist and antagonist muscles in fast human movements is characterized by a phasic pattern, normally composed by three bursts and known as the friphasicpatfern. The most important events of this pattern are the initial agonist activation (AGI) responsible for the initial limb acceleration, and the antagonist activation (AMI), coincident with the electrical silence of the agonist muscle. On last 15 years, a lot of experimental research was done to understand how the Central Nervous System programs ballistic movements performed at different speeds. The most part of these studies were done with single-joint movements, performed an laboratorial environments, which became more attractive as a paradigm for testing hypotheses but didn't allow direct applications to more complex and "natural" movements. Purposes of this study were (1) to characterize the activation pattern of agonist and antagonist muscles of elbow extension on a dart throw to a target, (2) to analyze the effects of movement velocity on EMG and cinematic parameters and (3) to compare the above mentioned variables on trained and untrained subjects. Experiments were performed on four skilled dart throwers and nine untrained subjects. The task was a dart throw to a concentric target at a distance of 3 m and 1,70 m of centre height. Each subject performed 30 trials on each of three different conditions. Subjects were instructed before each condition: (P) "try to reach the target centre", (C) "try to reach the target centre as fast as possible" and (V) '3ust try to be as fast as possible". Two electrogoniometers on shoulder and elbow joints were used to measure position and velocity movement parameters on each joint. Surface EMGs were recorded from triceps (vastus medialis) and biceps brachii with active bipolar electrodes. The EMG signals were filtered, fullwave rectified and smoothed. The angle, velocity and EMG signals were time normalized using the shortest movement time as a reference and averaged in blocks of 20 trials representatives of each condition. Then, the EMG bursts (AGI and ANT) were isolated for parameters determination. A laser system developed on our Faculty allowed the dart speed determination. The elbow extension on initial condition (P) were accomplished by a tri- or biphasic EMG pattern with a clear tendency for a reciprocal activation: the maximum peak of ANT was always coincident with the silent period between the two agonist bursts AG 1 was a short duration burst (90- 135 ms) which began before movement onset and ceased before the moment of elbow peak velocity. The antagonist pattern contained a phasic burst (ANT) which began before the end of AGl and presented its maximum peak near the end of the acceleration phase. This burst was normally preceded by a tonic activation which started near movement imitation. The results show that either the modulation on amplitude and timing of AGI can be seen together or separate when we compare different throwing conditions. The subjects adjusted the time and the size af the burst to the nature of the task with a possible individual predominance of one of these mechanisms. Nevertheless, the increase of the initial EMG slope, measured by the integrated EMG of the first 30 rns of AGI [iEMG30), revealed to be the most related variable with the elbow movement speed. This finding agrees with a "dual-strategy" model (Gottlieb et al., 1989a,b, 1990). The antagonist EMG presented identical timing structure between different throwing conditions, but revealed a general tendency to an increase on its intensity when subjects throw quickly. The similar behaviour of agonist and antagonist activation intensities suggests a common mechanism of magnitude control. The untrained subjects show longer acceleration phases and longer duration of EMG events (duration of AGl, time to agonist and antagonist EMG peak, time of antagonist onset) than the skilled throwers. Those trained subjects presented reduced variability on temporal structure among throwing conditions.


Ileal digestibility and availability of lysine in protein concentrates ,for pigs The availability of lysine in protein concentrates for pigs and the relationship between ileal digestibility and availability have been investigated in two separate research projects : Dr Jane Leibholz of the University of Sydney, with weaner pigs, and myself at the Wollongbar Agricultural Institute, using grower pigs. The findings have been published in two separate series of papers in the British Journal of Nutrition. The results and conclusions have been diametrically opposed; Dr Leibholz found that ileal digestibility and availability were similar, we found that ileal digestibility overestimated availability in heat-damaged meals. In her latest paper Dr Leibholz (1992) offers explanations for these differences and why her results differ from mine. I would like to offer readers alternative explanations. The major differences in our findings are summarized in Table 1, using soya-bean meal and cottonseed meal as examples of highand low-quality meals. They indicate: (1) both centres found similar values for the ileal digestibility of lysine in cottonseed meal (0.56-0.74) and soya-bean meal (0.88-0.92); (2) Dr Leibholz found the availability of lysine was similar to the ileal digestibility, we found the availability of lysine was similar to the ileal digestibility for soya-bean meal, but only about half the ileal digestibility for cottonseed meal; ( 3 ) Dr Leibholz reported high estimated retentions of absorbed lysine from cottonseed meal (0.94) which suggest that all the absorbed lysine was available, we found much lower retention (0.36), which indicates it wasn't! ; (4) Dr Leibholz also reported high retentions of absorbed methionine from soya-bean meal (0.98), again we found much lower retention (0.45); (5) both centres conducted experiments which they claimed validated their values. The results described were the basis for Dr Leibholz concluding that the ileal digestibility of amino acids reflected availability. We concluded that the ileal digestibility assay overestimated availability in heat-processed meals. Clearly both conclusions can't be right !


Sm,-The article " Youth Looks at General Practice," by Dr. C. P. D. Grant (Journal, April 30, p. 1049), should be read by every medical practitioner and senior medical student, for it expresses the views of the majority of young general practitioners. In a short space Dr. Grant reviews comprehensively the fears, problems, hopes, and subsequent thrill of success that result from the efforts of the general practitioner. I should like to stress several of his points and elaborate them. It is true that many of us on qualifying set as our ideal a specialty and rather unwillingly later turn to general practice as the permanent sphere of our work. Having arrived in general practice it is found that we are lacking in many of the essentials which are necessary to make a success of the job. We do not know what measles is like, and have never seen a patient suffering from diphtheria. In fact, many of us have never even seen a sore throat; and we certainly have never tried to treat one before. Neither do we appreciate the differences in approach which are necessary in the surgery and home, as compared to the hospital. We have not access to white cell counts and endless x-rays to aid our diagnosis. We have to diagnose perforated ulcers immediately after perforation and not six hours later, as the hospital staff can do. These defects show a grave lack of foresight in our medical education which is partly administrative and partly due to the teaching clinician. Those who arrange our curriculum and timetables have not yet fully appreciated the everwidening gulf between hospital practice and general practice, which has become so pronounced since the end of the war. Our teaching clinicians are composed more and more of younger men who, though brilliant in their own sphere, have little, if any, personal experience of general practice. As a result, they do not know what the medical student needs to be taught. The uses of cortisone and intravenous terramycin are of no great importance to the general practitioner; but which student has been taught how to treat influenza ? Learning the job takes time, but if we are willing and humble a great deal can be learnt quickly. Like Dr. Grant, I have had to learn to try to control a temper which I had not realized existed. But we must learn to endure fools; and also eccentric hospital consultants. There are consultants who will only do domiciliary visits on a Sunday afternoon, and those who will not do them outside a town except under pressure. These are in a minority, granted, but one cannot always do without their services. The majority fortunately are on extremely good terms with the general practitioner and are only too willing to help at any time. TIhe greatest satisfaction comes from being accepted as a family doctor, and as such I consider it is my duty to provide full maternity services to all my patients who request such services; and the majority prefer their own doctor to the clinics. I am glad we have no regulation in force in this part of the world like there is in Glasgow controlling admission to maternity beds. Here the general practitioner has equal access to beds as do the local authority clinics and those who attend the hospital clinics entirely. It seems to me that the local authority clinics for maternity care have largely outworn their usefulness in many areas, and could be dispensed with or curtailed. As Dr. Grant says, it is the general practitioner who has to deal with the antenatal emergencies, and not the clinic. Finally, let us realize that the patients themselves are mostly considerate and appreciative, often out of all proportion to the services rendered to them. But a word of advice to those who have not yet settled in practice-get out of the seaside resorts and wealthy residential areas, and practise in an honest-to-goodness working-class area, where there is more work, more appreciation, and more satisfaction to be gained.-I am, etc.,


For any given set-valued solution concept, it is possible to consider iterative elimination of actions outside the solution set. This paper applies such a procedure to define the concept of iterated monotone potential maximizer (iterated MP-maximizer). It is shown that under some monotonicity conditions, an iterated MP-maximizer is robust to incomplete information [A. Kajii, S. Morris, The robustness of equilibria to incomplete information, Econometrica 65 (1997) 1283-1309] and absorbing and globally accessible under perfect foresight dynamics for a small friction [A. Matsui, K. Matsuyama, An approach to equilibrium selection, J. Econ. Theory 65 (1995) 415-434]. Several simple sufficient conditions under which a game has an iterated MP-maximizer are also provided.


The η3-allymolybdenum complexes [Mo(C5H5)(CO)2(syn-1-C3H4R)](R = vinyl or buta-1,3-dienyl) undergo BF3 catalysed carbon–carbon bond formation with aldehydes, ketones and α,β-unsaturated ketones; applications to the synthesis of functionalized 1,3-dienes and 1,3,5-trienes are reported, and evidence for formation of an s-trans-diene as an intermediate is presented.


In a material of 10 osseointegrated implants of pure titanium, Tivanium, Vitallium, and stainless steel, 23 interface areas were studied by transmission electron microscopy. The implant site was the upper tibia of mature rabbits, and the observation time was 11 months. The absence of a cellular reaction was verified. However, even in cases of apparently uniform osseointegration, electron microscopy revealed an unpredictable variation in interface ultrastructure within 500-1,000 nm of the metal surface, common to all the materials. There was no structural feature that was specific for a particular material.


[1] Observations of waves and currents in a temperate reef environment off southwestern Western Australia over a period of 1 year reveal the relative importance of wind and wave forcing. During periods of low waves, linear regression analysis shows alongshore currents seaward and shoreward of the reef line are reasonably well predicted using 1% and 0.5% of the wind speed, respectively. However, shoreward of the reef line anomalously strong currents were often observed during periods of light or even opposing winds and the mean sea surface was elevated relative to offshore of the reefs. These anomalous currents and elevated sea level occur during periods of high waves and both are correlated with the root-mean-square wave height seaward of the reefs, similar to what has been observed in coral reef environments. The observations were simulated with the numerical model XBeach which includes radiation stress forcing due to the presence of the waves. The model was also used to examine the dynamics of the wave-driven flow in terms of the momentum balance. As on a coral reef, through the surf zone over the reef bottom, friction is balanced by the sum of the radiation stress gradient and pressure gradient. Away from the reefs the radiation stress gradients are small and the momentum balance is between bottom friction and pressure gradient.


This article has been retracted by IOP Publishing following an admission by the authors that this article contains significant similarities with another published paper [1]. IOP Publishing has investigated in line with the COPE guidelines, and agree that this article should be retracted. The authors have not commented on whether they agree or disagree with the retraction notice. [1] Nurtanto M, Widjanarko D, Sofyan H, Rabiman, Bruri Triyono M, 2019, Learning By Creating: Transforming Automotive Electrical Textual Material Into Visual Animation As A Creative Learning Products (CLP), IJSTR 8 10 Retraction published: 17 May 2022


Central venous catheters are useful for acute hemodynamic monitoring, fluid resuscitation, drug administration, the aspiration of air embolism and total parenteral nutrition. However, various complications may occur during central venous catheterization and the most common complication of the internal jugular approach is arterial puncture. Arterial puncture can be easily identified by a pulsatile blood flow and the bright red color of blood. It is usually confirmed by connecting catheter to a pressure transducer and observing venous waveforms and venous pressure. We experienced a patient in whom arterial carmulation was unrecognized by pressure recording, but was confirmed by blood gas analysis.


Abstract : Towards the end of 1955 the U.S. Army Medical Research Unit (USAMRU) began extensive collections of adult mosquitoes in Ulu Gombak Forest Reserve, Selangor. The mosquitoes were identified by one of us (W. W. M.) and the staff of the Division of Entomology of this Institute (I.M.R.), after which they were returned to USAMRU for attempted isolation of viruses. These catches were virtually the first regular forest collections in Malaya since Leicester's classical work at the beginning of the century (Leicester, 1908), and the problem which they immediately posed was one of taxonomy and nomenclature. Many of the species were unrepresented in the Institute collection, doubts often arose' over the correct identification of specimens, and, consequently, much of the material could be identified only to a species group. The position was aggravated by the fact that virologists require large numbers of mosquitoes alive, or very recently killed, for their virus isolation work, and entomologists prefer mosquitoes on pins for definitive identification. In the event, most of the identifications were done while the mosquitoes were alive: but representative specimens were put aside for more leisurely examination. It became clear from the adult catches of USAMRU that the mosquitoes of Ulu Gombak would repay closer study. Most species could not be separated satisfactorily with the existing keys, the larvae and males of many were unknown, and practically nothing was known of their breeding and biting habits. Following the recommendations of a conference on virus diseases held at the Institute for Medical Research in 1954 (Institute for Medical Research, Malaya, 1955), the investigation of those, and allied, problems has been a main concern of one of us (W. W. M.) for several years, and the following account is based principally on the collections of his unit.


The single fibre EMG differences during motor axonal stimulation at different firing rates were studied in myasthenic patients: 15 with, and 15 without thymoma. 10 healthy volunteers were also examined. Conventional repetitive stimulation EMG as well as SFEMG during weak voluntary contraction and on 10 and 20Hz stimulation was performed in every patient. The mean jitter in the control group was 30 microseconds on voluntary contraction and about 22 microseconds at 10 as well as at 20 Hz stimulation. In both groups of myasthenic patients under consideration SFEMG on voluntary contraction detected neuromuscular transmission disturbances of various degree. The results obtained at motor axonal stimulation (10 and 20 Hz) were unhomogeneous. In both groups jitter seemed to be slightly shorter at higher (20 HZ) frequency stimulation, probably due to facilitation but differences were insignificant.


Colorectal cancer (CRC) is one of the major causes of death in the developed world and forms a canonical example of tumorigenesis. CRC arises from a string of mutations of individual cells in the colorectal crypt, making it particularly suited for multiscale multicellular modeling, where mutations of individual cells can be clearly represented and their effects readily tracked. In this paper, we present a multicellular model of the onset of colorectal cancer, utilizing the cellular Potts model (CPM). We use the model to investigate how, through the modification of their mechanical properties, mutant cells colonize the crypt. Moreover, we study the influence of mutations on the shape of cells in the crypt, suggesting possible cell- and tissue-level indicators for identifying early-stage cancerous crypts. Crucially, we discuss the effect that the motility parameters of the model (key factors in the behavior of the CPM) have on the distribution of cells within a homeostatic crypt, resulting in an optimal parameter regime that accurately reflects biological assumptions. In summary, the key results of this paper are 1) how to couple the CPM with processes occurring on other spatial scales, using the example of the crypt to motivate suitable motility parameters; 2) modeling mutant cells with the CPM; 3) and investigating how mutations influence the shape of cells in the crypt.


Abstract The author illustrates squatting, do-it-yourself urbanism, creative re-appropriation of public space, guerrilla gardening, and artistic occupy-type intervention as forms and evolutions of informal urbanism. By interpreting examples observed in two postsocialist Romanian cities the author comments on the thin boundary between informal and authorized urbanism, and between creativity and power; he interrogates also the key matter of access to the city, with its regulations, resources, and potentialities. His perspective implies an empirical and ethnographic approach to informality, which is analysed in the contexts of privatization logics, especially in relation to the reconfiguration of the public and the private which is so specific to postsocialist transformations. The contrast between grass-roots responses and official projects is seen as decisive in understanding strategies of representations, control of resources, and capital accumulation. Additionally the author suggests the relevance of theorizing such postsocialist urban processes in fruitful but critical comparison with other non-Western forms of urbanism, notably postcolonial ones.


This paper presents an educational experience that includes the conceptual and the methodological elements of a course in Health and Culture that we have developed since 2006 in the Faculty of Nursing at the Pontificia Universidad Javeriana, Bogota, Colombia. The course integrates the analysis of the diversity of practices, knowledge, and institutions in health and disease, and the exploration of power as a determinant of diversity, inequalities and inequities related to gender, life stage, ethnicity, rural or urban origin, or social class. It describes the contents, methodologies and the course evaluation forms.


BACKGROUND
Treatment of neuropathic pain remains a challenge. The current study investigated the therapeutic effect of intrathecal administration of NF-kappaB antisense oligodeoxynucleotides (ODNs) on mechanical allodynia and thermal hyperalgesia in a chronic constriction injury (CCI) model of rats.

METHODS
Lumbar intrathecal catheters were implanted in male Sprague-Dawley rats and a CCI model was established. Thermal and mechanical nociceptive thresholds were assessed with paw withdrawal latency (PWL) to radiant heat and von Frey filaments. The phosphorothioate-modified antisense ODNs to p65 subunit of NF-kappaB were administered intrathecally on each of five consecutive days post-CCI. Nuclear NF-kappaB p65 expression was assessed by western blot.

RESULTS
CCI induced mechanical allodynia and thermal hyperalgesia and significantly increased NF-kappaB p65 protein expression. Intrathecal injection of antisense ODN markedly suppressed the expression of NF-kappaB p65 protein and significantly attenuated CCI-induced mechanical allodynia and thermal hyperalgesia.

CONCLUSION
The activation of NF-kappaB pathway may contribute to neuropathic pain in CCI rats. Suppression of NF-kappaB could be a potential new strategy for the treatment of neuropathic pain.


The high energy consumption of buildings in the various sectors of society, the exploitation of natural resources and the use of fossil fuels make it necessary to research constructive alternatives that can reduce the impact on the planet. The use of thermal insulation in buildings is important for the reduction of energy consumption, however, most of the materials developed are manufactured generating high rates of pollution. This study starts with the use of natural elements (corn cob / soybean straw / pine bark) and innovative elements (vacuum / slimstone plate), in order to improve energy efficiency of buildings. The methodological development of the work began in the selection of materials and development of facade cladding boards. The determination of the thermal conductivity was analyzed using a heating plate and PT100 temperature sensors, determination of the apparent and actual density, and analysis of the material composition using Scanning Electron Microscopy (SEM). After the development of the analyzes, the natural slabs and recycled slimstone showed significant results, with thermal conductivity lower than 0.07 W / m.k.


In this paper, we address the single image haze removal problem in a nighttime scene. The night haze removal is a severely ill-posed problem especially due to the presence of various visible light sources with varying colors and non-uniform illumination. These light sources are of different shapes and introduce noticeable glow in night scenes. To address these effects we introduce a deep learning based DeGlow-DeHaze iterative architecture which accounts for varying color illumination and glows. First, our convolution neural network (CNN) based DeGlow model is able to remove the glow effect significantly and on top of it a separate DeHaze network is included to remove the haze effect. For our recurrent network training, the hazy images and the corresponding transmission maps are synthesized from the NYU depth datasets and consequently restored a high-quality haze-free image. The experimental results demonstrate that our hybrid CNN model outperforms other state-of-the-art methods in terms of computation speed and image quality. We also show the effectiveness of our model on a number of real images and compare our results with the existing night haze heuristic models.


The ground aspects of phenomenological perspective provide a wide range of the literary study in collaboration with literary theories with the single exception of Marxism that cannot be studied better in the phenomenological perspectives; rather, in critical ones. The relationship of Marxism and literary theories with phenomenological common grounds is highlighted in the current study through descriptive method of research. The study illustrates this relationship of Marxism and literary theories in phenomenological perspectives considering the previous studies for which Jane Austen's Pride and Prejudice is taken as a sample. Keywords: Literary Theories; Marxism; Phenomenology


Pubic bones from 486 modern American females between the ages of 13 and 99 were studied in an attempt to explore the relationship between the degree of dorsal pitting and the following variables: (1) number of full term pregnancies, (2) inteval since last pregnancy, (3) age of decedent.A statistical association was found between the number of full term pregnancies and the degree of dorsal pitting. However, the correlation is not strong; 17 females reported as being nulliparous have "medium to large" dorsal changes whereas 22 females having from one to five full term pregnancies have an absence of dorsal changes. Females who had their last child 15 or more years prior to death are more apt to have "medium to large" dorsal changes than are females who have more recently given birth. This effect appears to be independent of the number of full term pregnancies, but is probably related to age. When the data are analyzed by multiple regression analaysis, it is found that age and number of pregnancies are most important in predicting the degree of pitting and the effect of the interval on pitting is not significant. Age is found to be an important variable independent of the number of full term pregnancies. In nulliparas, an absence of dorsal pitting is far more frequently found in females younger than 30 than in those over 30.


The visual system exploits prior knowledge on the world to disambiguate a scene. In particular, the inference of shape-fromshading relies on the fact that light comes from above our heads. Recent studies have helped make that assumption more precise and suggested that the preferred light source position was further biased on the left of the vertical. We investigated the generality of this result in two experiments with a different stimulus and a novel task. The stimulus was shaped like a ring (Polo Mint) divided in eight equal sectors. Depending on the assumed light source position, all sectors but one could be perceived as either convex or concave. In the first experiment, observers had to report the different shaped sector position (left or right side of the stimulus). In the second experiment, they had to classify the shape of the odd sector (convex or concave). Various amounts of blur were also applied on each stimulus. Results in both experiments confirm previous studies that observers prefer stimuli lit from the left rather than the right. We also demonstrate that left-lit stimuli give the observers a more sensitive perception of the shape of the objects. Finally, the second experiment confirms a preference for globally convex shapes, especially when the stimulus is severely blurred.


- Now a days, SMS-supported mobile searching applications are gradually more widespread around the globe, particularly in current scenario among users with low-end mobile devices. So, Web exploration is one of the main and valuable of these applications. SMS-supported web exploration takes unstructured queries and returns web snippets via SMS. This application permits users with low-priced mobile phones and no data plan to hit into the enormous amount of information on the web. SMS-supported web exploration is a demanding problem since the channel is both tremendously constricted and costly. Preferably, together the query and the response fit within an SMS. This paper presents the blueprint and execution of SMS Search, an SMS-supported search application that facilitates users to achieve exceptionally crisp (one SMS message) search responses for queries across random keywords in one round of communication. SMS Search is intended to balance existing SMS-supported search applications that are moreover inadequate in the keywords they identify or engage an individual in the loop. Specified an unstructured search query, "SMS Search", uses a usual search engine as a back-end to extract a number of search responses and uses a mixture of information retrieval procedures to take out the most suitable 140-byte snippet as the final SMS search reply. We illustrate that SMS Search returns suitable responses for 62.5% of Mahalo search queries in our experiment set; this precision rate is high given that Mahalo make use of a human to respond the identical queries. So we have also installed a pilot edition of SMS Search for make use of with a little featured group and a bigger scale open beta in Meerut to investigate our application and contribute to our understanding. In this paper I(we) depict my (our) algorithm to mine snippets for any given unstructured query of the form <query, clue>.


The advancement in internet-based learning technologies together with the national agenda towards globalized online education in Malaysia have prompted the learning management system (LMS) to become an important channel for institutions of higher education to effectively deliver education to students. Since user resistance has been known to be a stumbling block in the implementation of the LMS, it is crucial for the institutions to acknowledge that comprehensive adoption by users relies heavily on user acceptance. Moreover, since some institutions may have even made it compulsory for students to use the LMS, user acceptance of the LMS should be studied in the sense that using LMS is likable and pleasurable. Although the features of the technical capability of the LMS are important, it has been asserted that having the feeling of personal convenience when using the LMS is even more important to the users. With the amount of financial effort and manpower involved in implementing the LMS by institutions in Malaysia towards fulfilling the online learning agenda of the nation, it is important to study whether the convenience factor as an individual impact can play the partial role of influencing Malaysian students' satisfaction of the LMS which would in turn influence them to use the LMS. Based on the Information System Success Model by DeLone and McLean, this study establishes vital process factors regarding the LMS usage among university students in Malaysia. Hence, in this study, LMS usage by students is measured by the degree of students' acceptance of the LMS. An online survey has been done to collect data from 212 students of two large public universities in Malaysia. Structural equation modeling has been used to test the relationships in the conceptual model. The results of data analysis using the PLS-SEM technique employed in the study have indicated that student satisfaction is positively influenced by factors of information quality, system quality, service quality and convenience. LMS usage has been found to be positively impacted by student satisfaction while student satisfaction has been found to have significant mediation effect. The findings from this study can be utilized by institutions committed towards having successful implementation of the LMS. In enhancing LMS usage by the students, the institutions of higher education can consider focusing on the necessary steps towards increasing student satisfaction. Meanwhile, to increase student satisfaction, apart from improving the information quality, system quality and service quality, institutions should also seriously consider promoting the LMS to the students by highlighting the individual impact of the LMS in terms of convenience.


BACKGROUND
Pneumothorax (PNX) is a recognized cause of preventable deaths in trauma patients. Our objective was to determine the incidence of traumatic PNX, the characteristics of its victims, and the treatment they receive.

METHODS
The study consisted of data set of a population-based study on major trauma.

RESULTS
The incidence of PNX was 81 per 1 million population per year, mostly caused by transport accidents. PNX victims generally had multiple injuries, and they showed on-scene clinical parameters worse than victims of other chest injuries of comparable severity. Fifty-three percent of PNXs were drained during the prehospital and early (< 2 hours) hospital course. There was no uniformity of treatment among different types of rescue facilities, some of them never performing decompression despite clinical need. The z statistic for mortality was -0.63.

CONCLUSION
PNX can be expected in one in five major trauma victims found alive. PNX is associated with a peculiar on-scene instability. Early decompression is often required. The effects of wider access to prehospital decompression and the reasons for its uneven availability in our setting need elucidation. Nevertheless, the present mortality follows the international standards.


The chemical diversity of secondary metabolites in medicinal plant makes it a huge challenge to isolate the bioactive compounds from herbal extracts, so quick recognition of the bioactive ones is of vital importance for improving the efficiency of isolation. In this study, a ligand fishing experiment based on human serum albumin functionalized magnetic nano-particles (HSA-MNPs) was performed to probe the bioactive components in a traditional Chinese medicinal plant, Dioscorea panthaica. The minor compounds fished out by HSA-MNPs were identified by electrospray ionization mass spectrometry (ESI-MS), and then separated from the extract of the whole plant by one or two steps of column chromatography under the guidance of ESI-MS. Four biologically active compounds, progenin II, progenin III, dioscin and gracillin, were isolated much faster than in the normal lengthy phytochemical procedure. The present study demonstrates that biological macromolecule (protein, enzyme, receptor, et al.) functionalized MNPs may serve as baits to recognize bioactive small molecules in complex herbal extracts. It is expected that a macromolecule functionalized MNPs-based ligand fishing experiment coupled with ESI-MS may accelerate the process of identification and isolation of bioactive components from medicinal plants, and thus benefit the speed of drug discovery.


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In this talk, I would like to describe how some constructions from combinatorial game theory generalize to category theory, and how category theory may be useful to help analyze combinatorial games. I will begin by briefly describing combinatorial games, then discuss the notion of a "combinatorial game category", as well as give some interesting examples, and some ideas of how they may be useful.


A bipartition model for ion transport in solids has been presented. Unlike the earlier bipartition model, a single-scattering approximation has been adopted and angular correlation of energy transfer has been partly taken into account. By the present bipartition model, the reflection coefficients and energy spectrum of reflected ions have been calculated. The results show that the present bipartition model gives better descriptions of reflection although it is simpler in calculation than the earlier bipartition model.


In this paper, I discuss parents' accounts of personifying and memorialising their child through a visual and virtual lens. As an extension of a real world memorial such as a gravesite, a virtual mourning space provides a space for personal narratives that are not socially or legitimately endorsed by the social networks to which bereaved parents relate. Parents often struggle to respond to others 'awkward silences' or seeming insensitivities. Virtual mourning sites, thus, provide a space and location for narration about a deceased child and with it a sense of community building. Parents can attend to the dual process of grieving ( Stroebe and Schutt, 2001) by attending to life and society by 'putting on a brave face,' to then one of 'normality ' in a virtual world where expressions of grief are acknowledged and with it a sense of meaning which can be derived from an otherwise stigmatized self.


In the last decade, major breakthroughs in the understanding of genetic contributions to Parkinson's disease (PD) have been achieved. Recently, mutations in LRRK2, encoding dardarin, have been found to be responsible for an autosomal dominant parkinsonism (OMIM 607060). We screened 311 subjects (cases: n = 202, controls: n = 109) for the three previously reported LRRK2 mutations. Our investigation revealed a sporadic case of PD with a heterozygous mutation G2019S (c.6055G>A). Here, we present the clinical phenotype of this patient and discuss the implications of genetic testing for the G2019S mutation in patients with sporadic PD.


Mycobacterium tuberculosis (M. tb) is an intracellular pathogen persisting in phagosomes that has the ability to escape host immune surveillance causing tuberculosis (TB). Lipoarabinomannan (LAM), as a glycolipid, is one of the complex outermost components of the mycobacterial cell envelope and plays a critical role in modulating host responses during M. tb infection. Different species within the Mycobacterium genus exhibit distinct LAM structures and elicit diverse innate immune responses. However, little is known about the mechanisms. In this study, we first constructed a LAM-truncated mutant with fewer arabinofuranose (Araf) residues named M. sm-ΔM_6387 (Mycobacterium smegmatis arabinosyltransferase EmbC gene knockout strain). It exhibited some prominent cell wall defects, including tardiness of mycobacterial migration, loss of acid-fast staining, and increased cell wall permeability. Within alveolar epithelial cells (A549) infected by M. sm-ΔM_6387, the uptake rate was lower, phagosomes with bacterial degradation appeared, and microtubule-associated protein light chain 3 (LC3) recruitment was enhanced compared to wild type Mycobacterium smegmatis (M. smegmatis). We further confirmed that the variability in the removal capability of M. sm-ΔM_6387 resulted from host cell responses rather than the changes in the mycobacterial cell envelope. Moreover, we found that M. sm-ΔM_6387 or its glycolipid extracts significantly induced expression changes in some genes related to innate immune responses, including Toll-like receptor 2 (TLR2), class A scavenger receptor (SR-A), Rubicon, LC3, tumor necrosis factor alpha (TNF-α), Bcl-2, and Bax. Therefore, our studies suggest that nonpathogenic M. smegmatis can deposit LC3 on phagosomal membranes, and the decrease in the quantity of Araf residues for LAM molecules not only impacts mycobacterial cell wall integrity but also enhances host defense responses against the intracellular pathogens and decreases phagocytosis of host cells.


This paper proposes a new variational model for joint multiplicative denoising and deblurring. It combines a total generalized variation filter (which has been proved to be able to reduce the blocky-effects by being aware of high-order smoothness) and shearlet transform (that effectively preserves anisotropic image features such as sharp edges, curves and so on). The new model takes the advantage of both regularizers since it is able to minimize the staircase effects while preserving sharp edges, textures and other fine image details. The existence and uniqueness of a solution to the proposed variational model is also discussed. The resulting energy functional is then solved by using alternating direction method of multipliers. Numerical experiments showing that the proposed model achieves satisfactory restoration results, both visually and quantitatively in handling the blur (motion, Gaussian, disk, and Moffat) and multiplicative noise (Gaussian, Gamma, or Rayleigh) reduction. A comparison with other recent methods in this field is provided as well. The proposed model can also be applied for restoring both single and multi-channel images contaminated with multiplicative noise, and permit cross-channel blurs when the underlying image has more than one channel. Numerical tests on color images are conducted to demonstrate the effectiveness of the proposed model.


A buried pipe was installed using controlled low strength material (CLSM) as backfill as part of a study of installation procedures for buried pipe. A laboratory evaluation of mix designs was undertaken prior to the fieldtest to determine the suitability of the component materials and establish a mix with acceptable flow characteristics and a 28 day compressive strength of less than 1000 kPa (145 psi). The mix selected developed an average compressive strength of 334 kPa (48 psi) at 7 days and 600 kPa (87 psi) at 28 days, and Young's moduli of 120 MPa (17 ksi) at 7 days and 190 MPa (28 ksi) at 28 days. The field installation was in a trench with a width equal to the pipe outside diameter plus 600 mm. One length each of 900 mm nominal inside diameter concrete, corrugated steel and corrugated HDPE pipe was elevated on bags of gravel to allow the CLSM to flow under the pipe. The plastic and metal pipes were weighted with bags of gravel to minimize flotation. The CLSM was placed to the springline in two lifts, two hours apart. The metal pipe floated slightly while the second lift was being placed. Backfilling above the CLSM with a native clay commenced about 16 hours after installation of the CLSM. The CLSM provided excellent support for the pipe in especially hard to reach areas underneath the pipe. Pipe deflections were small and similar to those for the same pipe and high quality crushed stone backfill carefully placed and well compacted. Re-excavation of the installation about three weeks later showed that the CLSM backfill provided excellent support; however, excavation was difficult, even at that early age. A lowering of the target strength for the CLSM mix design to between 200 kPa and 400 kPa (30 psi and 60 psi) at 28 days is recommended for providing more excavatable backfill.


Aims Apolipoprotein A-1 (ApoA-1), based on epidemiology, is inversely associated with cardiovascular (CV) events. Human carriers of the ApoA-1 Milano variant have a reduced incidence of CV disease. Regression of atherosclerotic plaque burden was previously observed on intravascular ultrasound (IVUS) with ETC-216, a predecessor of MDCO-216. MDCO-216, a complex of dimeric ApoA-1 Milano and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine, is being developed to reduce atherosclerotic plaque burden and CV events. We investigated the efficacy and safety of a single infusion of MDCO-216 in healthy volunteers and in patients with coronary artery disease (CAD). Methods and results Twenty-four healthy volunteers and 24 patients with documented CAD received a 2-h infusion of MDCO-216 in a randomized, placebo controlled, single ascending dose study. Five cohorts of healthy volunteers and four cohorts of CAD patients received ApoA-1 Milano doses ranging from 5 to 40 mg/kg. Subjects were followed for 30 days. Dose-dependent increases in ApoA-1, phospholipid, and pre-beta 1 HDL and decreases in ApoE were observed. Prominent and sustained increases in triglyceride, and decreases in HDL-C, endogenous ApoA-1 and ApoA-II occurred at doses >20 mg/kg and profound increases in ABCA1-mediated cholesterol efflux were observed. Other lipid and lipoprotein parameters were generally unchanged. MDCO-216 was well tolerated. Conclusions MDCO-216-modulated lipid parameters profoundly increased ABCA1-mediated cholesterol efflux and was well tolerated. These single-dose data support further development of this agent for reducing atherosclerotic disease and subsequent CV events.


Sharland et al. (2001) define two tectonic mega-sequences on the Arabian Plate encompassing Late Cretaceous and Early Tertiary time—AP9 and AP10. These mega-sequences mark the transition of the Arabian Plate from a passive margin setting to a tectonically active margin located along its northeastern edge. Ophiolite obduction and the creation of a foredeep with rapid subsidence were key events. Despite the tectonically active nature of this interval of time, Sharland et al. (2001) recognize six plate-wide third-order sequences (K150, K160, K170, K180, Pg10, and Pg20) within the relevant preserved rock record, sequences that have been upheld in subsequent reviews of Arabian Plate sequence stratigraphy (e.g., Simmons et al., 2007). Figure 1 summarizes the depositional sequences present in mega-sequences AP9 and AP10 on the Arabian Plate and the generalized facies architecture.


Model-driven development (MDD) is a software engineering discipline which suggests that software development should be done at the modelling level and that applications should be generated from models. A key concept of MDD is a model transformation that generates software artifacts, such as code, from models. Since models are `first-class` citizens in MDD, their verification and validation are important tasks and so are the model transformations. A transformation contract, which is also a model, is a specification of what a particular model transformation must implement and essentially specifies a relation between metamodels and properties that must hold on such a relation. The authors have defined a design pattern that enforces transformation contract correctness over model transformations implementations. This study reports on (i) the proposed design pattern, (ii) the design of the UMLtoEJB model transformation that generates application code, following the Enterprise Java Beans standard, from class diagrams described in the Unified Modelling Language, and (iii) a discussion on how the transformation contracts approach may help different actors, in an MDD software development process with transformation contracts, to identify erroneous situations.


A60 The objective of this study was to investigate the influence of genetic variations in genes encoding doxorubicin metabolizing enzymes carbonyl reductases 1 and 3 ( CBR1 and CBR3 ) and ATP-binding cassette transporters ( ABCB1 and ABCC5 ) on the pharmacokinetics of doxorubicin in Asian breast cancer patients receiving adjuvant chemotherapy (N=48). Patients received doxorubicin (range: 56-61 mg/m 2 ) as a 20 minutes intravenous infusion and blood samples were collected at 0, 0.5, 1, 4, 8 and 24hrs. Non-linear mixed effect modeling was applied for the analysis of concentration-time profile of doxorubicin (NONMEM version 6). Doxorubicin pharmacokinetics was best described by a two-compartmental model, which included inter-individual variability (IIV) in terms of the fixed effect parameters [total plasma clearance (CL), the inter-compartmental clearance (Q) and the volume of distribution in central and peripheral compartments (V1 and V2)]. IIV was modeled based on an exponential relationship with fixed effect parameters and residual error model was described by the combination of additive and proportional equations. Model estimate for doxorubicin clearance (CL) was 44.7 L/h and inter-compartmental clearance (Q) was 46.8 L/h. The apparent volume of distribution in central compartment (V1) and peripheral compartment (V2) was 18.2 L and 537 L, respectively. Among the genetic and non-genetic covariates investigated, patient weight and CBR1 . 219G>C genotype showed significant associations with pharmacokinetics of doxorubicin. CBR3 which has minimal relative tissue expression compared to CBR1 did not show any influence on pharmacokinetics of doxorubicin. Weight alone explained 5.2% of inter-individual variability on doxorubicin clearance. The patients harbouring CBR1 . 219G>C observed 9% less clearance than the wild type (CL Lhr - 1: GG vs GC+CC: 48.2 ± 10.4 vs 41.8 ± 7.2; P = 0.03) and the exposure level was significantly higher in patients homozygous for the CBR1 . 219C allele (AUC μg hr L -1 : GG vs GC+CC: 1987 ± 376 vs 2275 ± 348.5; P = 0.045). The proposed population pharmacokinetic model incorporating patient weight and CBR1 genotype status explained 22% of total variability in the clearance of doxorubicin in Asian breast cancer patients. No significant association of genetic and non genetic covariates on the pharmacokinetic parameters of doxorubicinol was observed.


Mottled, blotched, fine-grained, unimpressive in the hand specimen, the ore in the Ag deposits in the little-known Mineral district near the Snake River in Washington County, Idaho, when viewed under the microscope, is found to possess extraordinary textural and structural features and a mineralogy that is unique to the state. The ore occurs as fillings and replacements along complex zones of fracturing in volcanic rocks of pre-Tertiary age and was formed close to the surface at temperatures mainly below 135 degrees C. Minerals, most of which are distinguishable and identifiable microscopically, include pyrite, marcasite, sphalerite, wurtzite, tetrahedrite, chalcopyrite, galena, and, in 1 deposit, also stannite, cylindrite, bournonite, and boulangerite. The Fe and Zn sulfides show globular and botryoidal development with radial and concentric structures indicative of colloidal deposition. Because of the influence of these colloform structures on the deposition of the other, noncolloidal minerals, and also because of the more or less selective replacement of the ore minerals by late calcite, the textural and structural relations of the ore are complicated and of more than usual interest. Abundant permeation and replacement by late calcite has been responsible for the mottled and blotched appearance of the ore. The Ag probably had its source in the tetrahedrite and galena; the ore mined in the past had probably been enriched in supergene silver sulfides.


A systematic methodology for solving the inverse dynamics of the Delta robot is presented.First,the inverse kinematics is solved based on the vector method.A new form of the Jacobi matrix formulized by the vectors is obtained so the three types kinematics singularities namely inverse, direct and combined types, can be identified with the physical meaning.Then based on the principle of virtual work, a methodology for driving the dynamical equations of motion is developed.Meanwhile the whole actuating torques, the torques caused by the gravity, the velocity and the acceleration are computed respectively in the numerical example. Results show that torque caused by the acceleration term is much bigger than the other two terms.This approach leads to efficient algorithms since the constraint forces and moments of the robot system have been eliminated from the equations of motion and there is no differential equation for the whole procedure when the principle of virtual work is applied to solving the inverse dynamical problem.


Obstetricians' epidemiological knowledge and their awareness of associated risk factors are essential for the primary prevention of birth defects. Screening and early diagnosis of congenital malformations is an expanding field in general obstetrics. Cardiac defects are the most frequent type of congenital malformation, and early detection is possible.


Contemporary discourses about children's use of information and communication technologies (ICT)—which both celebrate children's command of a technology which is seen to be our future, and raise fears that this technology is putting children's emotional well-being at risk—are problematic, resting as they do on essentialist ideas about children, and overt technological determinism. Drawing instead on work within the new social studies of childhood, and the sociology of science and technology, we identify a need for research which examines how children and technology come together in diverse communities of practice. The communities of practice we study are the home- and school-based ICT usage of British school children in the late 1990s. Our research identifies the different ways in which children and adults negotiate children's technical and emotional competence in relation to ICT, and uncovers the varied meanings of childhood and technology which emerge for adults and children in these two socio-spatial environments. These findings not only highlight the spatiality of children's and adults' performances and understandings of ICT competence, but also how these are constituted through the socio-spatial relations which shape the off-line spaces of home and school.


OBJECTIVE
In light of the current controversy about whether severe temper outbursts are diagnostic of mania in young children, we conducted a study to characterize such children, focusing on mania and other mood disorders, emotion regulation, and parental psychiatric history.

METHODS
Study participants included 51 5-9-year-old children with frequent, impairing outbursts (probands) and 24 non-referred controls without outbursts. Parents completed a lifetime clinical interview about their child, and rated their child's current mood and behavior. Teachers completed a behavior rating scale. To assess emotion regulation, children were administered the Balloons Game, which assesses emotion expressivity in response to frustration, under demands of high and low regulation. Parental lifetime diagnoses were ascertained in blind clinical interviews.

RESULTS
No child had bipolar disorder, bipolar disorder not otherwise specified (NOS), or major depression (MDD). The most prevalent disorder was oppositional defiant disorder (88.2%), followed by attention-deficit/hyperactivity disorder (74.5%), anxiety disorders (49.0%), and non-MDD depressive disorders (33.3%). Eleven probands (21.6%) met criteria for severe mood dysregulation. During the Balloons Game, when there were no demands for self-regulation, children with severe outbursts showed reduced positive expressivity, and also showed significant deficits in controlling negative facial expressions when asked to do so. Anxiety disorders were the only diagnoses significantly elevated in probands' mothers.

CONCLUSIONS
Overall, young children with severe temper outbursts do not present with bipolar disorder. Rather, disruptive behavior disorders with anxiety and depressive mood are common. In children with severe outbursts, deficits in regulating emotional facial expressions may reflect deficits controlling negative affect. This work represents a first step towards elucidating mechanisms underlying severe outbursts in young children.


In the past three decades, financial deregulation, or the process of removing governmental rules controlling the way that financial organizations operate, has facilitated interconnections between commercial real estate markets, the financial sector and national economic markets. As a result, commercial real estate has become an important 'financial' asset in the investment portfolios of both national and international investors. In this thesis I analyse different key aspects of the real estate market, including commercial real estate development, prices and locations in an era of financial deregulation and innovation. The first study shows that commercial and residential real estate developments complement each other in the long run. In the second study, I show the impact of credit availability on commercial real estate asset prices. I furthermore, show that investors are willing to pay a market liquidity premium. The results also show that investors accept a lower capitalization rate for office building associated with agglomeration economies. Finally, our results provide new empirical evidence on the premium that tenants are willing to pay for retail locations associated with tourism. The findings in this thesis help our understanding of various commercial real estate topics.


W279 use automatic speech recognition to assess spoken English learner pronunciation based on the authentic intelligibility of the learners' spoken responses determined from support vector machine (SVM) classifier or deep learning neural network model predictions of transcription correctness. Using numeric features produced by PocketSphinx alignment mode and many recognition passes searching for the substitution and deletion of each expected phoneme and insertion of unexpected phonemes in sequence, the SVM models achieve 82% agreement with the accuracy of Amazon Mechanical Turk crowdworker transcriptions, up from 75% reported by multiple independent researchers. Using such features with SVM classifier probability prediction models can help computer-aided pronunciation teaching (CAPT) systems provide intelligibility remediation.


Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL

Melanoma claims the lives of thousands of individuals each year despite the development of novel therapeutic agents. The vast majority of these deaths are due to cancer metastasis and prognosis in each case is often difficult to determine. This lack of effective therapy and prognostic indicators emphasize the need for a better understanding of the genetic and phenotypic changes in melanoma formation and progression. One such change may be the loss of E-cadherin, an important molecule in cell-cell adhesion. E-cadherin is downregulated with melanoma disease progression, suggesting that it may function to restrict melanoma invasion and metastasis. Though changes in E-cadherin expression have been suggested to be important in cancer progression in in vitro studies, few have investigated this change functionally in vivo. In order to characterize the role of E-cadherin in melanoma formation and metastasis, we have utilized a well-characterized conditional mouse model combining the Braf V600E mutation with Pten tumor suppressor loss. This model allows us to specifically and reproducibly induce melanoma in mice in a spatially and temporally restricted model. We have combined this model with conditional E-cadherin inactivation in order to evaluate the role of E-cadherin loss on changes in cell morphology and signaling in addition to melanoma formation, progression and metastasis. Loss of E-cadherin significantly decreases survival of mice in the Braf/Pten tumor model and alters the expression of markers of epithelial to mesenchymal transition (EMT). These findings functionally delineate the role of E-cadherin loss in melanoma formation and progression.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3377. doi:10.1158/1538-7445.AM2011-3377


While general publication practices clearly differ between disciplines, knowledge about scientometric indicators can also greatly vary. The observed heterogeneity in bibliometric knowledge inspired us to define the concept of 'metric-wiseness' for researchers. Being metric-wise can lead to an advantage for knowledgeable researchers over uninformed colleagues, even when they are of otherwise equal competence. We identify two paths through which metric-wiseness can play a role and lead to behavioural changes in the research process. As a first path, metric-wiseness can be seen as an additional tool that is useful in reporting one's research portfolio. A second one is more ambiguous and has some undesirable aspects, possibly diminishing intrinsic motivational factors for doing research. Innovation and innovative research slows down if crowding out happens due to an excessive attention to scientometric indicators. We propose an approach to actually measure metric-wiseness.


Platform-based product family design is recognized as an effective method to construct a product line that satisfies diverse performance requirements while aiming to keep design and production costs low. The success of the resulting product family often relies on properly resolving the tradeoff between increasing commonality across the family and performance loss compared to individual design. In this paper, a systematic approach is proposed to design the scale-based product family with multi-platforming configuration and it contributes in three aspects. Firstly, the effect of commonality on the related product life-cycle activities is evaluated in the platform decision to decide the expected degree of sharing for each design variable and thus generate the anticipated platform configuration. Secondly, unlike many existing methods that assumes a given single-platform, the proposed method addresses the multi-platforming configuration across the family, and can generate alternative product family settings with different levels of commonality. Finally, the product family design is formulated as a multi-optimization problem and solved using a modified genetic algorithm. An industrial example of a planetary gear train for cordless drills is presented to demonstrate the proposed method.


The enantioselective preparation of pharmacologically interesting chroman-fused spirooxindole derivatives is described based on an organocatalytic multicomponent cascade reaction. The compounds synthesized using this method potently inhibited the proliferation of various cancer cell lines. The most potent compound (7e) induced caspase-independent apoptosis and cell cycle arrest in MCF-7 breast cancer cells by interfering with the p53-MDM2 interaction and downstream pathways.


Composites based on acrylonitrile–butadiene rubber, carbon nanotubes, and manganese–zinc ferrite were fabricated and tested for electromagnetic interference (EMI) absorption shielding. First, carbon nanotubes and ferrite were solely used for the preparation of rubber composites. Then, carbon nanotubes were combined with magnetic filler and incorporated into the rubber matrix. The results revealed that carbon nanotubes act as reinforcing filler and significantly enhance the physical–mechanical properties of composites. The presence of carbon nanotubes in the rubber matrix also results in an outstanding increase in electrical conductivity and permittivity of composite materials, as a consequence of which the EMI absorption shielding was poor in the tested frequency range of 1 MHz to 3 GHz. On the other hand, ferrite-filled composites are able to efficiently absorb electromagnetic radiation emitted from various electronic and radiation sources. However, the tensile strength of the composites showed a decreasing trend with increasing content of ferrite. The combination of carbon nanotubes with manganese–zinc ferrite resulted in an improvement in the physical–mechanical properties of hybrid composites. As the permittivity of hybrid composites was still much higher in comparison with those filled only with ferrite, only the composite filled with 5 phr of carbon nanotubes and 100 phr of ferrite showed a slight EMI absorption shielding ability over the tested frequency range.


Zolpidem is a hypnotic agent used for the treatment of insomnia. In this study a stability indicating HPLC method was developed for the determination of zolpidem in the presence of its degradation products. Stress degradation of zolpidem was performed under acidic, alkaline, oxidative, heat and photolytic conditions. Separation of zolpidem and its degradation products were performed on a Nova-Pak CN column using KH2PO4 30 mM and acetonitrile (65: 35, v/v at pH 6) as mobile phase. Acceptable linearity (r 2 >0.999) and precision (CV value <1.5%) were achieved over the concen- tration range of 1-20 g/mL. Degradation of zolpidem was observed under acidic, alkaline, oxidative conditions and also exposure to UV light. The proposed method was used for assay determination of zolpidem tablets with no interfering from excipients.


The study focuses on the phylogenetic origin and genetic diversity of brown trout in the eastern part of the Balkan Peninsula. It further aims to reveal the impact of human-mediated transfers and stocking with non-indigenous trout on the populations in this area. For these purposes, mtDNA control region and microsatellite variation of 204 individuals from 16 populations were analysed. The results indicate that mtDNA haplotypes from the lower Danube basin and southern Black Sea basins differ substantially from a subclade of the Danubian lineage consisting of haplotypes found so far in the most of the Danube basin and in the Caspian and Aral Sea basins. Considering also the results of demographic analyses, this study evidences a complex evolutionary history of brown trout in the southern and western parts of the Black Sea basin. In the Aegean Sea basin, a high frequency of the central haplotype of Adriatic mtDNA lineage has been found. The other Adriatic lineage haplotypes found in this basin differ from the central haplotype by one mutational step only, indicating a recent evolution of the Adriatic lineage in the Aegean Sea basin. Substantial genetic differentiation among populations and basins was revealed. The hybridization with Atlantic brown trout was indicated in both sea basins, but especially in the Danube basin. Compared to other European regions, it can be inferred that the introgression of exogenous brown trout in the eastern Balkan populations is rather low.


Purpose – The main aim of this paper is to build an equivalent circuit model of a comb drive microactuator, while the phenomenon of generating the electric fringing field at electrode edges is taken into consideration.Design/methodology/approach – The approach to the comb drives design requires the "leakage capacitance" (appearing at electrode edges) to be introduced to the complex equivalent circuit model. Introducing these capacitances leads to defining the circuit model properly.Findings – Such a complex approach by use of the equivalent circuits model could make it possible to reduce the discrepancy between the field and circuit models. These results were obtained after comparing both field and circuit models.Originality/value – MEMS microdrives are in the area which is being developed very dynamically. Improvements in the mathematical models would permit more precise microdrive design, leading to optimal structure.


Fulton and MacPherson introduced the notion of bivariant theories related to Riemann-Roch-theorems, especially in the context of singular spaces. This is powerful formalism, which is a simultaneous generalization of a pair of contravariant and covariant theories. Natural transformations of bivariant theories are called Grothendieck transformations, and these generalize a pair of ordinary natural transformations. But there are many situations, where such a bivariant theory or a corresponding Grothendieck transformation is only "partially known": characteristic classes of singular spaces (e.g. Stiefel-Whitney or Chern classes), cohomology operations (e.g. singular Adams Riemann-Roch and Steenrod operations for Chow groups) or equivariant theories (e.g. Lefschetz RiemannRoch). We introduce in this paper a simpler notion of partial (weak) bivariant theories and partial Grothendieck transformations, which applies to all these examples. Our main theorem shows, that a natural transformation of covariant theories, which commutes with exterior products, automatically extends uniquely to such a partial Grothendieck transformations of suitable partial (weak) bivariant theories ! In the above geometric situations one has for example to consider only morphisms, whose target is a smooth manifold, or more generally, a suitable "homology manifold" (and in the general bivariant language this is related to the existence of suitable strong orientations). We illustrate our main theorem for the examples above, relating it to corresponding known Riemann-Roch theorems.


Background In RA, congestive heart failure (CHF) is an important contributor to the excess mortality. Some traditional CHF risk factors are overrepresented in RA, but they do not completely explain the risk (1). Inflammatory cytokines are suggested to contribute to development of myocardial dysfunction (1). RA patients have had unexplained diffuse myocardial abnormality at autopsy more frequently than controls (2). At autopsy, citrullination has been been higher in the myocardium of RA compared to other diseases, suggesting a link between autoimmunity and the increased prevalence of myocardial dysfunction in RA (3). To our knowledge, only few cardiac magnetic resonance (CMR) studies in RA patients have been published. One such study showed high prevalence of late enhancement (LGE) of the myocardium, associated with high mean disease activity score (DAS)28 (4). Objectives We aimed to assess myocardial abnormalities in patients with active RA without cardiac symptoms by contrast enhanced CMR. Methods Fifty-four RA patients and 12 patients with fibromyalgia (FM) underwent CMR. RA group comprised 29 patients with newly diagnosed RA starting treatment with disease modifying anti-rheumatic drugs (DMARDs) and 25 patients with chronic active RA starting biological therapy. Contrast enhanced CMR was performed to analyze LGE of the myocardium. The location, pattern and extent of LGE were analyzed using American Heart Association (AHA) 17-segment model. Results Mean age (SD) was 50 (12) years in RA patients and 54 (12) in FM patients. Myocardial LGE was detected in 34 RA patients (63%) and in one FM patients (p<0.001). One RA patient with newly diagnosed RA had subendocardial and circular LGE typical for cardiac amyloidosis. One patient exhibited lateral transmural LGE indicating infarct scar. Otherwise pattern on LGE was non-specific. LGE presented midmyocardial and subepicardial pattern in most cases and was predominantly located in the basal and inferior or inferolateral regions of left ventricle. In RA patients, myocardial LGE correlated with DAS28, CRP (p=0.049). Conclusions Myocardial LGE evaluated with CMR is a common finding in patients with active RA without cardiac symptoms. Myocardial LGE shows correlation to disease activity in RA. References Giles JT et al. Myocardial dysfunction in rheumatoid arthritis: Epidemiology and pathogenesis. Arthritis Res Ther. 2005. Koivuniemi R et al. Cardiovascular diseases in patients with rheumatoid arthritis. Scand J Rheumatol. 2013. Giles JT et al. Myocardial citrullination in rheumatoid arthritis: A correlative histopathologic study. Arthritis Res Ther. 2012. Kobayashi Y et al. Assessment of myocardial abnormalities in rheumatoid arthritis using a comprehensive cardiac magnetic resonance approach: A pilot study. Arthritis Res Ther. 2010. Acknowledgements This study was supported by grants from Helsinki University Central Hospital Research Funds and the Finnish Medical Foundation. Disclosure of Interest None declared


Objective To determine the safety and efficacy of the drug used. To analyze drug utilization pattern. To identify the ADR's caused by psychotropic drugs Methods: IRB approval was obtained and a hospital based cross sectional study was carried out at psychiatric OPD of OHRC. 500 prescriptions were collected and information was recorded in data collection form and analyzed. Results: From 500 prescriptions, 46.8% of prescriptions were of males and 53.2% of prescriptions were of females. Schizophrenia accounted for 29.6% of prescriptions whereas, 38.4% were of mood disorder, 21.6% were of anxiety and 10.4% were of other disorders.Drug Utilization Pattern in different psychiatric disorders : Mood disorder was the most common diagnosis followed by schizophrenia and anxiety. In mood disorder, the most commonly prescribed drug was escitalopram and the least commonly prescribed drug was fluoxetine. In schizophrenia the most commonly prescribed drug was diazepam and the least commonly prescribed drug was aripiprazole. In anxiety, the most commonly prescribed drug was clonazepam and the least commonly prescribed drug was haloperidol. PDD/DDD ratio of escitalopram and sodium valproate was nearer to one. Conclusion: In this study we get to know about the current prescribing trend of the psychotropic drugs and we also came to know the corresponding ADR'S of the drugs prescribed.


Background Various surgical treatments are described in the literature for biceps pathology. Method The techniques currently described for subpectoral tenodesis involve the use of suture anchors, interference screws, bicortical suture buttons or unicortical suture buttons. Results A review of 31 patients with a subpectoral biceps tenodesis using the anterior cortical button technique is presented. Conclusions We describe a novel technique, which provides an opportunity to obtain a robust cortical and intramedullary tenodesis, performed under direct vision without the risk of drilling the far cortex and therefore avoiding any potential for neurological injury. There is no cortical implant, which may lead to a diaphyseal stress riser and subsequent fracture risk.


Descriptive analysis methode of research describes about increasing subject in the level of critical thinking skills of students in solving mathematics based on 21st-century skills. The subjects research were 28 students of Mathematics Education Study Program at Ibrahimy University of Situbondo. Data collection is done by providing pre-test and study documentation to students. The test is given to collect data related to students' critical thinking skills. Then learning is done based on 21st-century skills. Furthermore, students are given a post-test solving mathematical problem. Data were collected through observations, test results and interview data tested for their validity by triangulation. The data analysis technique used is qualitative descriptive data analysis. The results of this study indicate that: (1) the results of the achievement of indicators of critical thinking of students based on critical thinking stages formulated by Facione, overall the subject of an increase of 7.53%; (2) there was the same highest increase in the achievement of the indicator thinking Facione stage, namely at the Analyze stage (A) for high, medium, and low category subjects respectively, 77.78%, 80%, and 44.44%. However, there are still two stages of critical thinking that still need attention for further research, namely at the List (L) and Self-Correct (S) stages classified as still needing special attention in implementing 21st-century skills in learning activities; (3) the level of critical thinking skills of students based on the critical thinking stages formulated by Facione was in the category of "not critical" for the pre-test results and was in the category of "sufficient critical" for the post-test results.


Examines the vital mechanisms of human communication, speech and hearing, through a discussion of the body's role in these functions.


In this article, we experiment with the idea of combining path dependency, convergence and contingency in explaining Finnish distinctiveness in education policy and politics since the early 1990s. The focus of this article is on quality assurance and evaluation (QAE) in comprehensive schooling. We elaborate on and contextualise the Finnish QAE model by analysing the particular and somewhat ambiguous ways in which global QAE practices have – or have not – been received and mediated in Finland.


BACKGROUND
Serious illness will inevitably lead to a fundamental emotional reaction. Traditionally, in interventional treatment or rehabilitation trials, the psychological status of patients with implantable cardioverter defibrillators has been evaluated with anxiety and depression as outcome measures. In caring for these patients, the aim of nursing is to help patients manage life with complex heart disease. The early detection and management of negative emotional response might prevent the development of pathological conditions such as depression.

OBJECTIVE
The aims of this study were to (a) describe the trajectory of primary emotions over time in patients with implantable cardioverter defibrillators and (b) examine the potential effects of psychoeducational nursing on primary emotions.

METHODS
During the inclusion period (October 2007 to November 2009), 196 patients with implantable cardioverter defibrillator were randomized (1:1) to rehabilitation versus usual care. Rehabilitation consisted of a psychoeducational nursing component and an exercise training component. This article concerns phase 1, psychoeducational nursing, guided by a theory of nursing, Rosemary Rizzo Parses Human Becoming Practice Methodologies. The outcome measure is the Emotions and Health Scale. The scale consists of 8 primary emotions: joy, agreeableness, surprise, fear, sadness, disgust, anger, and anticipation.

RESULTS
Mean (SD) age was 58 (13) years, and 79% of the participants were men. Significant improvements were found in primary emotional responses over time (P < .05) when combining groups. However, no difference in emotional intensity was found between the groups after 3 months of psychoeducational nursing intervention (P > .05).

CONCLUSIONS
Primary emotions are affected after implantable cardioverter defibrillator implantation. Improvements over time were found. However, it was not possible to detect any effect of a short-term psychoeducational nursing intervention. Evaluating the primary emotions might be a good way for nurses to monitor patients' psychological outcomes because the instrument is sensitive to changes over a short period. Further development of early psychoeducational nursing interventions for patients with implantable cardioverter defibrillators is needed.


Terahertz (THz) sensing has been developed over the past three decades for concealed weapons detection, medical imaging, and non-destructive evaluation; however methods for THz image exploitation have not been well reported. We test a multiscale image fusion algorithm for the 2011 IEEE National Aerospace and Electronics Conf. (NAECON) Grand Challenge which consists of Terahertz (THz) and visual images. The study consists of image characterization (signals distribution), image processing (data fusion), and image analysis (edge detection). We found that THz image characterization did not necessarily follow a distinct Gaussian distribution, THz imagery fusion with visual data supported target detection, and that image analysis enhanced target assessment. For the initial experiment, we assess the target segmentation through edge detection, image fusion results, and image fusion quality assessment. The preliminary image exploitation and fusion results can further develop THz collection over clothing-obscured concealed weapons imaging, parameter optimization, and targeting evaluation.


Severe congenital neutropenia (SCN) is an immunodeficiency characterized by disturbed myelopoiesis and an absolute neutrophil count (ANC) <0.5 × 109/L. SCN is also a premalignant condition; a significant proportion of patients develop myelodysplastic syndrome or leukemia (MDS/L). Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative treatment for SCN.


We propose stress management behavior, exercise, and scheduled sleep to represent the general intention and actual practices aimed to relieve stress by the application of the transtheoretical model (TTM). Randomly selected Chinese adults aged 18 - 64 were tested through an internet survey. The stage distributions for the three health behaviors were different across the Chinese adults. Stress was significantly higher in action and maintenance stages than in precontemplation and contemplation stages across three health behaviors. Our findings have provided preliminary findings on the applicability of TTM on the three health behaviors in Chinese adults with evidence of concurrent criterion validity.


We looked for pathogenic MECP2 mutations in 11 families with an index case affected by Rett syndrome (RTT), together with a sib or other relative affected by RTT or a less specific developmental disturbance. In one family, we detected the same MECP2 mutation in two affected sisters and their unaffected mother, who was subsequently shown to have skewed X chromosome inactivation. In five families, one affected subject was found to have a MECP2 mutation, but the other relative in whom a diagnosis of RTT was suspected, did not carry this or any other detectable MECP2 mutation. In the remaining five families, no MECP2 mutation was detected in any subject. These results suggest that familial RTT is rare and may be overdiagnosed. Furthermore, and despite the small probability of recurrence, many relatives of females with the usual, sporadic RTT may seek genetic testing to clarify their situation.

Rett syndrome (RTT) is a neurodevelopmental disorder that mostly affects females and is usually sporadic. It has therefore often been considered to be an X linked dominant condition with male lethality, although it is now recognised that de novo mutations in RTT occur predominantly on the paternally derived X chromosome and this could lead to similar observations.1–4 It is an important cause of profound mental handicap in girls, accounting for up to 10% of all cases. The diagnosis is currently based upon the clinical criteria proposed by the Rett Syndrome Working Group in 1988.5 The major criteria are: (1) normal pre- and perinatal period and apparently normal development for the first 6 months of life, (2) a period of regression occurring at 6 months to 3 years of age, (3) deceleration in head growth, (4) acquisition of stereotypical hand movements, and (5) eventual profound developmental delay. In addition, there are a …


Uganda's economic growth since the late 1980s has resulted largely from restoring and rehabilitating the country's productive capacity. Going forward, growth will need to come increasingly from new investments or new activities. That will require more investment, more intensive acquisition of know-how, and more complex collaboration between local and foreign partners. It will also require a far greater role for private sector investment. While Uganda has benefited enormously from development assistance for almost two decades, foreign aid may decline in the next decade. Indeed, Uganda must accelerate private sector investment and growth if it is to achieve the goals set out in its Poverty Eradication Action Plan. To reduce the poverty rate to 10 percent by 2017, GDP growth will have to exceed 7 percent a year, requiring an investment rate of 30 percent or more of GDP. Attaining these targets will be feasible only with reforms to promote private investment.


A study about coccidiosis in Japanese quails was carried out in order to identify species of the genus Eimeria and characterize a naturally occurring infection in a commercial rearing farm. For this purpose, fecal exams, oocyst counting and morphological study were performed, besides necropsy and histopathology to confirm diagnosis. Three species of the genus Eimeria were found and identified as E. tsunodai, E. uzura and E. bateri. The natural infection was characterized as subclinical because of the mild and nonspecific clinical signs. Nevertheless, coccidiosis was considered an important disease because endogenous stages of the parasites and a high number of oocysts in feces were associated with intestinal lesions. The results suggest that such infection might represent a limiting factor to this branch of the modern poultry industry.


An engineered thermal management is fundamental to the application of gas foil bearings (GFBs) as turboshaft supports in rotorcraft propulsion systems. The paper presents a model for the thermal energy transport in a rotor-GFB system operating at high temperature with typical inner and/or outer cooling flows. Predicted film temperatures agree with published test data, demonstrating the effectiveness of an outer cooling stream to remove heat and to control the operating temperature. The inner flow stream is not as efficient. The analysis shows paths of thermal energy by conduction and convection to assist in the design and troubleshooting of rotor-GFB systems operating hot. Bearing temperatures and shaft motions measurements are obtained in a test rotor electrically heated to 132°C. In speed-up tests to 26 krpm, the rotor motion amplitude drops suddenly just above the critical speed, thus, evidencing the typical hardening of compliant bearings. At the hottest test condition, since air is more viscous, the rotor peak motion amplitude decreases, not showing a jump. The coastdown tests show the critical speed increases slightly as the temperature increases.


: The paper reports the results of examination of 93 patients with rheumatic fever and 42 healthy children aged 10-13 on treatment at Evpatoria sanatorium under different weather conditions. In unfavourable weather (hypoxic, spastic) vegetative regulation underwent changes dependent on clinical condition of the child and initial vegetative status. Sanatorium treatment and conditioning inhibited sensitivity to meteorological factors in rheumatic children by 60 and in healthy children by 83%.


An overview of the state of the art in the direct oxygen or nitrogen insertion to aromatic rings and side-chains by hydroxylation, acetoxylation, partial oxidation and ammoxidation is presented. The influence of a variety of catalysts and oxidants on the yields of hydroxylated products of aromatic species is discussed in more detail. The survey is also focussed on the usage of H2O2 as an effective oxidising agent for hydroxylation reactions. Acetoxylation of methyl-substituted aromatic compounds to their corresponding esters in a single step is indeed an interesting area from an industrial point of view. Hence, the topics covering benzylic acetoxylation, although they are under a developmental stage for commercial exploitation, are also reviewed. The present contribution also covers the main directions of selective oxidation/ammoxidation of aromatic compounds to useful products, surveys recent developments and provides an updated discussion of the state of the art in the field of oxidation and ammoxidation of aromatics. Additionally, a comparative study of the vapour phase oxidation and ammoxidation of different alkyl aromatics to their corresponding aldehydes and nitriles using various heterogeneous catalysts is presented. Besides, the achievements and limitations of the catalysts/processes are emphasised. Furthermore, the present article includes a discussion of common features and differences in mechanistic steps of oxidation and ammoxidation reactions investigated by in situ FITR spectroscopy. The influence of acid-base properties of catalyst surfaces in connection with electronic effects of the substituents on the performance of the catalysts is also described.


Many fields of the industrial automation can be already served by wireless technologies. Due to the different requirements regarding the reliability, latency, number of nodes, node density and range to communication systems there is no uniform standard for wireless communication covering all domains of automation. It is to be expected in the future on a strongly increasing number of radio technologies and protocol stacks on different platforms and operating systems. According to this uniform integration interfaces neither exist on the side of the radio technologies nor on that of classical control systems. For relaying between both systems the architecture and the structure of a convergence middleware are presented, which abstracts the technology-specific details and makes a uniform integration interface available for wireless industrial communication systems. Furthermore a system is presented, with which the integration of wireless technology into automation systems can be automated and thus contributes to the decrease of complexity.


Incarcerated students face a number of additional challenges to those faced by most other students studying at a distance. Lack of internet access is especially problematic for those studying in a sector that is increasingly characterised by online and flexible course offerings. In this paper, we report on a project that will attempt to address the digital challenges that hinder prisoner access to higher education and provide inclusive learning experiences for incarcerated students. The trial utilises mobile yet secure digital technologies – namely Stand-Alone Moodle (SAM) and e-book readers – to improve access to resources. It is being trialled with a small sample of incarcerated students participating in the Studying to Succeed course within the Tertiary Preparation Program (TPP) at the University of Southern Queensland (USQ). We discuss the current provision of higher education in prisons and the challenges resulting from increased reliance on mobile learning technologies in higher education generally. The potential of the trial project to address the digital divide experienced by incarcerated students as compared to the general student population will also be discussed. It is hoped that students will be participating in learning experiences more closely related to those experienced by students outside of the prison system and they will be acquiring e-literacy and e-research skills. In addition, USQ will be fulfilling its obligation in relation to equity of access; and will be addressing the Australian Government's agenda of increasing participation in higher education by socially and economically disadvantaged groups.


Immune checkpoint inhibitors (ICI) improve patient survival in some cancer types but yield limited success in breast cancer. Phase-III clinical trials in triple-negative breast cancer (TNBC) patients, who harbor extensive tumor-infiltrating lymphocytes, demonstrate increased progression-free survival (IMpassion130) and pathologic complete response (KEYNOTE-522). Consequently, combinations of ICI and chemotherapy have been FDA-approved for metastatic TNBC patients. However, the therapeutic benefit of ICI alone and the most efficacious chemotherapy combinations are poorly characterized. We sought to model ICI response in vivo to elucidate the mechanisms of immunotherapy efficacy in breast cancer and ascertain the therapeutic benefits of different chemotherapeutic combinations with ICI.Using an immunocompetent EMT6 orthotopic mammary tumor model, we investigated the efficacy of single-agent immunotherapy and in combination with standard-of-care chemotherapy (paclitaxel [PAC] or doxorubicin [DOX]). We used single-cell RNA sequencing and bulk RNA and T-cell receptor (TCR) sequencingto assess the cellular landscape of the primary tumor in response to combinatorial therapeutic strategies and identify systemic genetic alterations and T-cell expansion, respectively.Single-agent anti-PD-L1 robustly suppressed primary tumor growth (p =0.0046) and extended survival (p<0.0001) beyond the isotype control. Chemotherapy demonstrated moderate therapeutic efficacy without potentiating the benefit of single-agent anti-PD-L1. Interestingly, despite using a genetically identical murine tumor model/host, anti-PD-L1 induced heterogeneous responses, from complete response to intrinsic resistance. Longitudinal analysis of peripheral blood from heterogeneously responding mice uncovered myeloid cell recruitment signatures corresponding to transient responses ultimately converting to resistance. We identified specific clonal T cell expansion present only in responders. Single-cell transcriptomic profiling of the tumor microenvironment revealed increased T cells and natural killer cells and reduced regulatory T cells in the combination groups versus chemotherapy alone, although this did not translate into improved benefit. Gene-set enrichment analysis on infiltrating T cells identified a robust signature of cytotoxic T cell activation characterized by a significant enrichment in inflammatory pathways in both single-agent anti-PD-L1 and in combination with chemotherapy.We identify a heterogeneously ICI-responsive in vivo model that emulates TNBC patient response to combinatorial ICI approaches. We describe single-agent ICI efficacy in upregulating cytotoxic immune cell infiltration and expansion within the primary tumor that diminishes tumor growth and enhances survival. Moreover, this study describes differential responses in a genetically similar host, which reflects heterogeneous patient response to ICI. Further characterization may identify systemic biomarkers and tumor antigen-specific T cell clones to accurately predict immunotherapy response in patients and uncover mechanisms for sensitizing refractory tumors to ICI