Cdk1 Restrains NHEJ through Phosphorylation of XRCC4-like Factor Xlf1

Eukaryotic cells use two principal mechanisms for repairing DNA double-strand breaks (DSBs): homologous recombination (HR) and nonhomologous end-joining (NHEJ). DSB repair pathway choice is strongly regulated during the cell cycle. Cyclin-dependent kinase 1 (Cdk1) activates HR by phosphorylation of key recombination factors. However, a mechanism for regulating the NHEJ pathway has not been established. Here, we report that Xlf1, a fission yeast XLF ortholog, is a key regulator of NHEJ activity in the cell cycle. We show that Cdk1 phosphorylates residues in the C terminus of Xlf1 over the course of the cell cycle. Mutation of these residues leads to the loss of Cdk1 phosphorylation, resulting in elevated levels of NHEJ repair in vivo. Together, these data establish that Xlf1 phosphorylation by Cdc2(Cdk1) provides a molecular mechanism for downregulation of NHEJ in fission yeast and indicates that XLF is a key regulator of end-joining processes in eukaryotic organisms.

U.S. teens in our world : understanding the health of U.S. youth in comparison to youth in other countries /

"This chartbook is the product of the efforts of many authors and editors, including Mary Overpeck ... [et al.]"--P. 16.

Monitoring dendritic cells in clinical practice using a new whole blood single-platform TruCOUNT assay

Dendritic cells (DC) from distinct DC subsets are essential contributors to normal human immune responses. Despite this, reliable assays that enable DC to be counted precisely have been slow to evolve. We have now developed a new single-platform flow cytometric assay based on TruCOUN(TM) beads and the whole blood Lyse/No-Wash protocol that allows precise counting of the CD14(-) blood DC subsets: CD11c(+)CD16(-) DC, CD11c(+)CD16(+) DC, CD123(hi) DC, CD1c(+) DC and BDCA-3(+) DC. This assay requires 50 mul of whole blood; does not rely on a hematology blood analyser for the absolute DC counts; allows DC counting in EDTA samples 24 It after collection; and is suitable for cord blood and peripheral blood. The data is highly reproducible with intra-assay and inter-assay coefficients of variation less than 3% and 11%, respectively. This assay does not produce the DC-T lymphocyte conjugates that result in DC counting abnormalities in conventional gradient-density separation procedures. Using the TruCOUNT assay, we established that absolute blood DC counts reduce with age in healthy individuals. In preliminary studies, we found a significantly lower absolute blood CD11c(+)CD16(+) DC count in stage III/IV versus stage I/II breast carcinoma patients and a lower absolute blood CD123(hi) DC count in multiple myeloma patients, compared to age-matched controls. These data indicate that scientific progress in DC counting technology will lead to the global standardization of DC counting and allow clinically meaningful data to be obtained. (C) 2003 Elsevier B.V. All rights reserved.

Executive control of working memory in schizophrenia

There is considerable evidence that working memory impairment is a common feature of schizophrenia. The present study assessed working memory and executive function in 54 participants with schizophrenia, and a group of 54 normal controls matched to the patients on age, gender and estimated premorbid IQ, using traditional and newer measures of executive function and two dual tasks-Telephone Search with Counting and the Memory Span and Tracking Task. Results indicated that participants with schizophrenia were significantly impaired on all standardised measures of executive function with the exception of a composite measure of the Trail Making Test. Results for the dual task measures demonstrated that while the participants with schizophrenia were unimpaired on immediate digit span recall over a 2-min period, they recalled fewer digit strings and performed more poorly on a tracking task (box-crossing task) compared with controls. In addition, participants with schizophrenia performed more poorly on the tracking task when they were required to simultaneously recall digits strings than when they performed this task alone. Contrary to expectation, results of the telephone search task under dual conditions were not significantly different between groups. These results may reflect the insufficient complexity of the tone-counting task as an interference task. Overall, the present study showed that participants with schizophrenia appear to have a restricted impairment of their working memory system that is evident in tasks in which the visuospatial sketchpad slave system requires central executive control. (c) 2005 Elsevier Ireland Ltd. All rights reserved.

Optimization of microcavity OLED by varying the thickness of multi-layered mirror

We optimized the emission efficiency from a microcavity OLEDs consisting of widely used organic materials, N,N'-di(naphthalene-1-yl)-N,N'-diphenylbenzidine (NPB) as a hole transport layer and tris (8-hydroxyquinoline) (Alq(3)) as emitting and electron transporting layer. LiF/Al was considered as a cathode, while metallic Ag anode was used. TiO2 and Al2O3 layers were stacked on top of the cathode to alter the properties of the top mirror. The electroluminescence emission spectra, electric field distribution inside the device, carrier density, recombination rate and exciton density were calculated as a function of the position of the emission layer. The results show that for certain TiO2 and Al2O3 layer thicknesses, light output is enhanced as a result of the increase in both the reflectance and transmittance of the top mirror. Once the optimum structure has been determined, the microcavity OLED devices can be fabricated and characterized, and comparisons between experiments and theory can be made.

Deploying internet commerce in lottery businesses:an executive guideline

Commerce is essentially the exchange of goods and services in various forms between sellers and buyers, together with associated financial transactions. Electronic Commerce (EC) is the process of conducing commerce through electronic means, including any electronic commercial activity supported by IT (information technology) (Adam and Yesha, 1996; Kambil, 1997; Yen, 1998). In this sense, EC is not totally new. Industries have used various EC platforms such as advertising on TV and ordering by telephone or fax. Internet Commerce (IC), or Web Commerce, is a specific type of EC (Maddox, 1998; Minoli D. and Minoli E., 1997). While some traditional EC platforms such as TV and telephone have been used to build “TV-gambling” and “telephone-betting” systems for conducting lottery business, Internet Lottery Commerce (ILC) has been assessed as the most promising type of EC in the foreseeable future. There are many social and moral issues relating to the conduct of lottery business on-line. However, this chapter does not debate these but deals only with business and technology issues. The purpose of this chapter is to provide a structured guide to senior executives and strategic planners who are planning on, or interested in, ILC deployment and operation. The guide consists of several stages: (1) an explanation of the industry segment’s traits, value chain, and current status; (2) an analysis of the competition and business issues in the Internet era and an evaluation of the strategic resources; (3) a planning framework that addresses major infrastructure issues; and (4) recommendations comprising the construction of an ILC model, suggested principles, and an approach to strategic deployment. The chapter demonstrates the case for applying the proposed guideline within the lottery business. Faced with a quickly changing technological context, it pays special attention to constructing a conceptual framework that addresses the key components of an ILC model. ILC fulfils the major activities in a lottery commerce value chain—advertising, selling and delivering products, collecting payments for tickets, and paying prizes. Although the guideline has been devised for lottery businesses, it can be applied to many other industry sectors.

Acoustic emission detection using optical fibre sensors for aerospace applications

Structural Health Monitoring (SHM) ensures the structural health and safety of critical structures covering a wide range of application areas. This thesis presents novel, low-cost and good-performance fibre Bragg grating (FBG) based systems for detection of Acoustic Emission (AE) in aircraft structures, which is a part of SHM. Importantly a key aim, during the design of these systems, was to produce systems that were sufficiently small to install in an aircraft for lifetime monitoring. Two important techniques for monitoring high frequency AE that were developed as a part of this research were, Quadrature recombination technique and Active tracking technique. Active tracking technique was used extensively and was further developed to overcome the limitations that were observed while testing it at several test facilities and with different optical fibre sensors. This system was able to eliminate any low frequency spectrum shift due to environmental perturbation and keeps the sensor always working at optimum operation point. This is highly desirable in harsh industrial and operationally active environments. Experimental work carried out in the laboratory has proved that such systems can be used for high frequency detection and have capability to detect up to 600 kHz. However, the range of frequency depends upon the requirement and design of the interrogation system as the system can be altered accordingly for different applications. Several optical fibre configurations for wavelength detection were designed during the course of this work along with industrial partners. Fibre Bragg grating Fabry-Perot (FBG-FP) sensors have shown higher sensitivity and usability than the uniform FBGs to be used with such system. This was shown experimentally. The author is certain that further research will lead to development of a commercially marketable product and the use of active tracking systems can be extended in areas of healthcare, civil infrastructure monitoring etc. where it can be deployed. Finally, the AE detection system has been developed to aerospace requirements and was tested at NDT & Testing Technology test facility based at Airbus, Filton, UK on A350 testing panels.

Estimation of ocular volume from axial length

Background/aims - To determine which biometric parameters provide optimum predictive power for ocular volume. Methods - Sixty-seven adult subjects were scanned with a Siemens 3-T MRI scanner. Mean spherical error (MSE) (D) was measured with a Shin-Nippon autorefractor and a Zeiss IOLMaster used to measure (mm) axial length (AL), anterior chamber depth (ACD) and corneal radius (CR). Total ocular volume (TOV) was calculated from T2-weighted MRIs (voxel size 1.0 mm3) using an automatic voxel counting and shading algorithm. Each MR slice was subsequently edited manually in the axial, sagittal and coronal plane, the latter enabling location of the posterior pole of the crystalline lens and partitioning of TOV into anterior (AV) and posterior volume (PV) regions. Results - Mean values (±SD) for MSE (D), AL (mm), ACD (mm) and CR (mm) were −2.62±3.83, 24.51±1.47, 3.55±0.34 and 7.75±0.28, respectively. Mean values (±SD) for TOV, AV and PV (mm3) were 8168.21±1141.86, 1099.40±139.24 and 7068.82±1134.05, respectively. TOV showed significant correlation with MSE, AL, PV (all p<0.001), CR (p=0.043) and ACD (p=0.024). Bar CR, the correlations were shown to be wholly attributable to variation in PV. Multiple linear regression indicated that the combination of AL and CR provided optimum R2 values of 79.4% for TOV. Conclusion - Clinically useful estimations of ocular volume can be obtained from measurement of AL and CR.

Analysis of purchasing activity with discounted cash flow inventory models = Beszerzési tevékenység elemzése diszkontált pénzáramlású készletmodellel

A klasszikus tételnagyság probléma két fontosabb készletezési költséget ragad meg: rendelési és készlettartási költségek. Ebben a dolgozatban a vállalatok készpénz áramlásának a beszerzési tevékenységre gyakorolt hatását vizsgáljuk. Ebben az elemzésben a készpénzáramlási egyenlőséget használjuk, amely nagyban emlékeztet a készletegyenletekre. Eljárásunkban a beszerzési és rendelési folyamatot diszkontálva vizsgáljuk. A költségfüggvény lineáris készpénztartási, a pénzkiadás haszonlehetőség és lineáris kamatköltségből áll. Bemutatjuk a vizsgált modell optimális megoldását. Az optimális megoldást egy számpéldával illusztráljuk. = The classical economic order quantity model has two types of costs: ordering and inventory holding costs. In this paper we try to investigate the effect of purchasing activity on cash flow of a firm. In the examinations we use a cash flow identity similar to that of in inventory modeling. In our approach we analyze the purchasing and ordering process with discounted costs. The cost function of the model consists of linear cash holding, linear opportunity cost of spending cash, and linear interest costs. We show the optimal solution of the proposed model. The optimal solutions will be presented by numerical examples.

“Acham que brotamos das fontes dessa cidade?”: uma etnografia sobre o cotidiano de sobrevivência de pessoas em situação de rua em Nata/RN

Through participant observation, held in the administrative region east of Natal / RN, this research aimed to understand about the daily life of men and women living on the streets in the city. How they relate to the space where they live? In this relationship, which uses and survival strategies triggered by this social segment? These were some of the questions that guided this research, in order to highlight the specificities of this way of life and the possible consequences that such a situation could reverberate. In this sense, there was an effort to keep up with people on the streets, their itineraries and seize their narratives. Along the search path - which took place intermittently between the years 2011-2015 - attended spaces of occupation and traffic of this population group in the street, as well as insert me and got involved in events, forums, seminars, meetings and subject of joints on the streets as a political movement (MNPR / RN). They are considered in this study as people on the street to those who occupy the street as their main space of survival and ordering of daily life: in the streets sleep, feed themselves, meet the physiological and hygienic needs, and is where draw sustenance. The street is taken in this research in its broadest sense, including all possible places relatively protected from the cold, rain and exposure to violence, thus includes both open and public spaces: as squares and parks; but also closed and private places: hostels, abandoned warehouses, prisons, etc. It was observed that in none of these spaces guys on the street are established in a fixed manner, in contrast, they experience the roaming, which in part is due to urban systems - which tends to stigmatize them and delete them places - and the very need to survive, because while living in the street differentiated practices are triggered, and these differ from the dominant mode of sedentary life.

“Acham que brotamos das fontes dessa cidade?”: uma etnografia sobre o cotidiano de sobrevivência de pessoas em situação de rua em Nata/RN

Through participant observation, held in the administrative region east of Natal / RN, this research aimed to understand about the daily life of men and women living on the streets in the city. How they relate to the space where they live? In this relationship, which uses and survival strategies triggered by this social segment? These were some of the questions that guided this research, in order to highlight the specificities of this way of life and the possible consequences that such a situation could reverberate. In this sense, there was an effort to keep up with people on the streets, their itineraries and seize their narratives. Along the search path - which took place intermittently between the years 2011-2015 - attended spaces of occupation and traffic of this population group in the street, as well as insert me and got involved in events, forums, seminars, meetings and subject of joints on the streets as a political movement (MNPR / RN). They are considered in this study as people on the street to those who occupy the street as their main space of survival and ordering of daily life: in the streets sleep, feed themselves, meet the physiological and hygienic needs, and is where draw sustenance. The street is taken in this research in its broadest sense, including all possible places relatively protected from the cold, rain and exposure to violence, thus includes both open and public spaces: as squares and parks; but also closed and private places: hostels, abandoned warehouses, prisons, etc. It was observed that in none of these spaces guys on the street are established in a fixed manner, in contrast, they experience the roaming, which in part is due to urban systems - which tends to stigmatize them and delete them places - and the very need to survive, because while living in the street differentiated practices are triggered, and these differ from the dominant mode of sedentary life.

Sistema inteligente para o processamento de imagens digitais intrabucais oclusais

Several are the areas in which digital images are used in solving day-to-day problems. In medicine the use of computer systems have improved the diagnosis and medical interpretations. In dentistry it’s not different, increasingly procedures assisted by computers have support dentists in their tasks. Set in this context, an area of dentistry known as public oral health is responsible for diagnosis and oral health treatment of a population. To this end, oral visual inspections are held in order to obtain oral health status information of a given population. From this collection of information, also known as epidemiological survey, the dentist can plan and evaluate taken actions for the different problems identified. This procedure has limiting factors, such as a limited number of qualified professionals to perform these tasks, different diagnoses interpretations among other factors. Given this context came the ideia of using intelligent systems techniques in supporting carrying out these tasks. Thus, it was proposed in this paper the development of an intelligent system able to segment, count and classify teeth from occlusal intraoral digital photographic images. The proposed system makes combined use of machine learning techniques and digital image processing. We first carried out a color-based segmentation on regions of interest, teeth and non teeth, in the images through the use of Support Vector Machine. After identifying these regions were used techniques based on morphological operators such as erosion and transformed watershed for counting and detecting the boundaries of the teeth, respectively. With the border detection of teeth was possible to calculate the Fourier descriptors for their shape and the position descriptors. Then the teeth were classified according to their types through the use of the SVM from the method one-against-all used in multiclass problem. The multiclass classification problem has been approached in two different ways. In the first approach we have considered three class types: molar, premolar and non teeth, while the second approach were considered five class types: molar, premolar, canine, incisor and non teeth. The system presented a satisfactory performance in the segmenting, counting and classification of teeth present in the images.

Sistema inteligente para o processamento de imagens digitais intrabucais oclusais

Several are the areas in which digital images are used in solving day-to-day problems. In medicine the use of computer systems have improved the diagnosis and medical interpretations. In dentistry it’s not different, increasingly procedures assisted by computers have support dentists in their tasks. Set in this context, an area of dentistry known as public oral health is responsible for diagnosis and oral health treatment of a population. To this end, oral visual inspections are held in order to obtain oral health status information of a given population. From this collection of information, also known as epidemiological survey, the dentist can plan and evaluate taken actions for the different problems identified. This procedure has limiting factors, such as a limited number of qualified professionals to perform these tasks, different diagnoses interpretations among other factors. Given this context came the ideia of using intelligent systems techniques in supporting carrying out these tasks. Thus, it was proposed in this paper the development of an intelligent system able to segment, count and classify teeth from occlusal intraoral digital photographic images. The proposed system makes combined use of machine learning techniques and digital image processing. We first carried out a color-based segmentation on regions of interest, teeth and non teeth, in the images through the use of Support Vector Machine. After identifying these regions were used techniques based on morphological operators such as erosion and transformed watershed for counting and detecting the boundaries of the teeth, respectively. With the border detection of teeth was possible to calculate the Fourier descriptors for their shape and the position descriptors. Then the teeth were classified according to their types through the use of the SVM from the method one-against-all used in multiclass problem. The multiclass classification problem has been approached in two different ways. In the first approach we have considered three class types: molar, premolar and non teeth, while the second approach were considered five class types: molar, premolar, canine, incisor and non teeth. The system presented a satisfactory performance in the segmenting, counting and classification of teeth present in the images.

How Much Greater Than the Sum of Its Parts? Evaluating Interactions Between Complex Policies

This presentation focuses on methods for the evaluation of complex policies. In particular, it focuses on evaluating interactions between policies and the extent to which two or more interacting policies mutually reinforce or hinder one another, in the area of environmental sustainability. Environmental sustainability is increasingly gaining recognition as a complex policy area, requiring a more systemic perspective and approach (e.g. European Commission, 2011). Current trends in human levels of resource consumption are unsustainable, and single solutions which target isolated issues independently of the broader context have so far fallen short. Instead there is a growing call among both academics and policy practitioners for systemic change which acknowledges and engages with the complex interactions, barriers and opportunities across the different actors, sectors, and drivers of production and consumption. Policy mixes, and the combination and ordering of policies within, therefore become an important focus for those aspiring to design and manage transitions to sustainability. To this end, we need a better understanding of the interactions, synergies and conflicts between policies (Cunningham et al., 2013; Geels, 2014). As a contribution to this emerging field of research and to inform its next steps, I present a review on what methods are available to try to quantify the impacts of complex policy interactions, since there is no established method among practitioners, and I explore the merits or value of such attempts. The presentation builds on key works in the field of complexity science (e.g. Anderson, 1972), revisiting and combining these with more recent contributions in the emerging field of policy and complex systems, and evaluation (e.g. Johnstone et al., 2010). With a coalition of UK Government departments, agencies and Research Councils soon to announce the launch of a new internationally-leading centre to pioneer, test and promote innovative and inclusive methods for policy evaluation across the energy-environment-food nexus, the contribution is particularly timely.

Synthetic lethal targeting of oncogenic transcription factors in acute leukemia by PARP inhibitors

Acute myeloid leukemia (AML) is mostly driven by oncogenic transcription factors, which have been classically viewed as intractable targets using small molecule inhibitor approaches. Here, we demonstrate that AML driven by repressive transcription factors including AML1-ETO and PML-RARα are extremely sensitive to Poly (ADP-ribose) Polymerase (PARP) inhibitor (PARPi), in part due to their suppressed expression of key homologous recombination genes and thus compromised DNA damage response (DDR). In contrast, leukemia driven by MLL fusions with dominant transactivation ability is proficient in DDR and insensitive to PARP inhibition. Intriguing, depletion of an MLL downstream target, Hoxa9 that activates expression of various HR genes, impairs DDR and sensitizes MLL leukemia to PARPi. Conversely, Hoxa9 over-expression confers PARPi resistance to AML1-ETO and PML-RARα transformed cells. Together, these studies describe a potential utility of PARPi-induced synthetic lethality for leukemia treatment and reveal a novel molecular mechanism governing PARPi sensitivity in AML.