Extensive world-wide studies in cancer epidemiology throughout most of this century have led to a generally accepted view that as much as 80-90% of all human cancer has its origins in environmental factors in our diet and lifestyle. Although in most cases several factors are likely to combine to produce a particular disease, the real significance of the above conclusion is its corrollary, that identification and elimination of these environmental factors should reduce the incidence of the disease. During this time period the incidence of most forms of cancer has remained essentially constant with one notable exception, lung cancer. Mortality from this disease has risen inexorably to its present epidemic proportions during the last seventy years and now accounts for the death of some 26000 men and 15 000 women each year in England and Wales alone. There is now no doubt that this is a direct result of cigarette smoking, and it is reliably predicted that abandonment of the habit would reduce this death rate ten-fold. The causes of other major forms of cancer, such as breast cancer in women and colon cancer in both sexes, have proved to be much more elusive. Their origins are probably complex and they are more difficult to study because there are no natural 'controls' as there are with lung cancer, where direct comparisons may be made between smokers and non-smokers. All possibilities for their causation are now under active consideration, and among them the influence of endogenous carcinogens generated by aberrant metabolism within the host is unknown, but cannot be discounted. It is now established that carcinogens of varied types are elaborated by both plants and microorganisms, and there seems to be no a priori reason why animals should not be similarly afflicted. Since most cancers are primarily diseases of old age it would seem unlikely that there would be strong evolutionary pressure against this happening. The idea that carcinogens, arising from steroids by incorrect metabolism, might be important in the induction of human cancer was a view commonly held in the past, but which has been neglected in recent times. Over fifty years ago, at the very outset of research into chemical carcinogenesis, the potent poly cyclic aromatic hydrocarbon carcinogen 3-methylcholanthrene was prepared by simple chemical transformations from a bile acid derivative. The correct structures for the bile acids and sterols were themselves established at about the same time, and the synthesis of this carcinogen took on an exaggerated importance in the minds of scientists. The enduring idea that methylcholanthrene formed by incorrect bile acid or sterol metabolism in the body might prove to be a cause of human cancer led to numerous attempts to identify this carcinogen in tumours and other tissues, but without success. The reason for this failure now seems obvious because experience has shown that cyclization of the sterol side chain does not occur to provide a fifth fused ring. Instead this side-chain tends to be lost with migration of the angular methyl groups, leading to compounds of the simpler four-ring cyclo-penta[a]phenanthrene series. These compounds thus possess the same basic carbon ring system as the steroids, but lack the angular methyl groups which characterize the latter. They are therefore capable of complete dehydrogenation to fully aromatic phenanthrene derivatives, and compounds of this type do in fact occur widely in petroleum and in oil-bearing shales as well as in river and lake sediments; they are also found in cooking oils that have been overheated. Advances in our understanding of oestrogen biosynthesis and metabolism have moreover suggested a plausible route by which cyclopenta[a]phenanthrenes might be formed in the body, but so far no attempts have been made to test this possibility. The need for further investigations in this area using modern techniques is now apparent, because numerous cyclopenta[a]phenan-threnes have since been synthesized and some have been shown to be strong carcinogens, similar in potency to the classical poly cyclic hydrocarbon carcinogen benzo[a]pyrene. This book is concerned with the occurrence, chemical synthesis, physical and chemical properties, and biological attributes of cyclo-penta[a]phenanthrenes. These are discussed in detail, as is their history which is intimately connected with the establishment of the correct structure of steroids. Interesting structure /carcinogenicity relationships, similar to those found among related polycyclic aromatic systems such as the chrysenes and benzo[a]anthracenes, are examined in relation to the metabolism of these compounds and the interactions of their metabolites with biological macromolecules. The book also lists physical data for nearly 350 cyclopenta[a]phenanthrene derivatives and contains exhaus- tive references to the original literature. It is hoped that it will provide a useful point of departure for those concerned with the possibility of the involvement of cyclopenta[a]phenanthrenes in the aetiology of human disease.


The Miyazawa-Jernigan (MJ) contact potential for globular proteins is a widely used knowledge-based potential. It is well known that MJ's contact energies mainly come from one-body terms. Directly in the framework of the MJ energy for a protein, we derive the one-body term based on a probabilistic model, and compare the term with several hydrophobicity scales of amino acids. This derivation is based on a set of native structures, and the only information of structures manipulated in the analysis is the contact numbers of each residue. Contact numbers strongly correlate with layers of a protein when it is viewed as an ellipsoid. Using an entropic clustering approach, we obtain two coarse-grained states by maximizing the mutual information between coordination numbers and residue types, and find their differences in the two-body correction. A contact definition using sidechain centers roughly estimated from C atoms results in no significant changes.


Purpose. Recent reports of torpedo maculopathy have disclosed underlying irregularities within the chorioretinal tissue that have not been shown to induce disturbances in visual function. Optical coherence tomography (OCT) provides a unique means of assessing the chorioretinal organization and integrity of torpedo lesions in an in vivo setting that has yet to be explored. In agreement with reported cases, torpedo maculopathy appears to be a benign, non-progressive condition that subtends the horizontal raphe in the juxtafoveal region and imparts no disturbance in visual function. Case Reports. Three cases of torpedo maculopathy were examined using Stratus OCT3 imaging (Carl Zeiss Meditec, Dublin, CA). OCT scans revealed intact, attenuated retinal layers with hyper-reflectivity of the retinal pigmented epithelium (RPE). The RPE subtending these lesions appears of normal thickness, yet, there is an abrupt transition between intact-organized and intact-disorganized retinal tissue in scans transitioning from normal retina to torpedo lesions. Our imaging studies revealed significant attenuation and disorganization of the inner and outer retinal layers overlying a hyper-reflective RPE, which was of normal thickness and devoid of any structural defects. Conclusions. An analysis of the OCT images collected suggests anomalies in retinal architecture. This finding implies that these lesions may represent atypical colobomas whereby retinal tissues are present but, perhaps, not fully developed. In light of these imaging studies, we propose that this uncommon condition may arise from deficits in cellular migration and/or organization.


This study aimed at evaluating under the users view, the quality structure and quality process of some services in an Emergency Care Unit of a university hospital. Fifty-fi ve clients/users took part in the survey when they were admitted in the unit and were waiting for an examination. Data were collected from December 2007 to March 2008, using a questionnaire and treated in the structure and process categories, increased of the Positivity Index (PI) for each sub item and average Positivity Index for each item/service. The items to which was given higher PI were the conditions of cleaning, feeding and safety regarding medical care and nursing; the lower PI was attributed to the physical space, number of workers and communication/interaction between customers and professionals. It was concluded, in the overall aspects that, the quality of services obtained a 'Satisfactory' level, however, to reach the "Excellent" quality (highest quality aspects of the structure and workers' performance), must be improved. Descriptors: Quality Assurance, Health Care; Health Services Evaluation; Hospital Care.


Preventing Graft-versus-Host Disease (GvHD) without impairment of immune reconstitution is a major goal in HLA-mismatched hematopoietic stem cell transplantation (HSCT). Many experimental strategies to selectively destroy or remove alloreactive donor T cells after allostimulation prior to infusion have been explored. An alternative approach is costimulatory blockade (CSB) during ex vivo allostimulation of donor T cells, rendering allospecific T cells within the donor cell pool alloanergized (i.e hyporesponsive to subsequent alloantigenic challenge). Murine and human data suggest effective induction of alloanergy by ex vivo CSB may involve an active cell-mediated suppression process requiring the presence of CD4+ CD25+ regulatory T cells (Tregs). We conducted a pilot clinical study of haploidentical HSCT after allospecific CSB with anti-B7.1 and -B7.2 antibodies and measured reconstitution of Treg by intracellular flow cytometry. 5 patients (pts; 4 high risk acute lymphoblastic leukemia, one marrow failure) underwent cyclophosphamide/TBI-conditioned haploidentical HSCT with cyclosporine and methotrexate as GvHD prophylaxis. Donor bone marrow was incubated with irradiated recipient peripheral blood mononuclear cells and 10μg anti-B7.1/2 antibodies/106 cells for 48 hours to induce alloanergy, washed and infused. All pts engrafted. All evaluable patients had a marked relative increase in peripheral blood CD4+ FOXP3+ T cells at D+20-60 (Figure 1). CD4+ FOXP3+ cells were CD25+ CD45RO+ intracellular CTLA4+ CD127lo consistent with a memory Treg phenotype. Treg were predominantly negative for HLA DR differentiating them from activated T cells. Despite receiving high doses of mismatched donor T cells (median 1.8 (CD4) and 3.1 (CD8) x 10 7 /kg) and all pts achieving 100% donor chimerism, only 2 pts developed acute GvHD, both Grade II, resolving after short courses of corticosteroids. All evaluable patients also had an increase in CD4+ T effector (Teff) cells with an activated phenotype (CD25+ HLA DR+ FOXP3-) at D+30-50. Pts had very rapid immune reconstitution (CD4, CD8, NK and CD8-CMV-tetramer+ cell numbers and immunoglobulin levels) and have had normal vaccination responses. 2 pts died, at D+35 (bacterial sepsis) and D+71 (multi-organ failure), both without GvHD. 3 pts survive (median follow up 5 years) with normal performance status with no chronic GvHD or disease relapse. Conditioning-related cytokine secretion may have led to reversal of anergy in vivo and expansion of alloreactive cells within the Teff cell population. The marked in vivo expansion of Treg may represent one mechanism of suppression of alloreactive Teff and subsequent immunological control of acute GvHD without impairing immune reconstitution in pts receiving HLA-mismatched donor T cells after ex vivo allospecific CSB. We are using a modification of this strategy in a clinical trial of delayed infusion of escalating doses of alloanergized donor T cells after CD34-selected haploidentical HSCT, to determine the optimal dose of alloanergized donor T cells that controls acute GvHD without impairment of immune reconstitution.


Recent studies have reported potential roles of angiotensins in an adaptative physiological mechanism of protection against cerebral ischemia-induced neurological damages. In the present study, we examined the protective role of angiotensin IV (AngIV) in a rat model of embolic stroke induced by intracarotid injection of calibrated microspheres (50 microm). Internal carotid infusions of increasing doses of AngIV (0.01, 0.1 and 1 nmol/0.1 mL saline) dose dependently decreased mortality, neurological deficit and cerebral infarct size at 24 hours. With the highest dose of AngIV, mortality was reduced from 55 % in saline infused controls to 10 % (p=0.003), neurological deficit was reduced from 3.8 +/- 0.3 to 1.4 +/- 0.3 , (p<0.0001) and cerebral infarct size at 24 hours was decreased from 432 +/- 26 mm(3) to 185 +/- 19, (p=0.0001). The AT(4) antagonist divalinal-AngIV (10(-9) mol/0.1 mL), or pretreatment with L-NAME (10(-7) mol/0.1 mL), both completely abolished the protective effect of AngIV (1 nmol). The AT(2) antagonist PD123319 (10(-7) mol/0.1 mL) partially prevented the protective effect of AngIV on the neurological score. Sequential cerebral arteriographies revealed that AngIV induced a redistribution of blood flow to the ischemic areas within minutes. These results suggest that pharmacological doses of AngIV are protective against acute cerebral ischemia by triggering an AT(4)-mediated, NO-dependent intracerebral hemodynamic mechanism.


Over the past decade, the world has witnessed significant changes in global and national polities. These changes, which include the re-emergence of semi-authoritarian regimes have had a substantial effect on the space for civil society advocacy. In Uganda, there has been an undulation between the promising eras of democratization in the 1990s to low days of oppressive legislations and institutions since 2005. What these changes dictate is that stakeholders working within and outside of the state ought not only to change their approach and strategies to cope with the changes in the rules of engagement but also win and sustain their operating space. This paper explores strategies employed by civil society actors to win and sustain space for operation in Uganda's semi-authoritarian setting. The analysis is situated in Uganda's Semi-Dominant Neo-Patrimonial Space, characterized by patronage and party dominance. Two case studies from civil society advocacy have been explored to delineate key lessons for civil society advocacy across the world. The case studies are presented in periodized interactions between the state and NGOs in order to contrast the outcomes of different strategies which predominated in different eras. The evidence presented shows that where civil society organizations and actors used more collaborative strategies and techniques in their advocacy, they achieved advocacy results and goals. One the other hand, where civil society engaged through less collaborative and confrontational strategies, they did not achieve results. It follows from the analysis therefore that in semi-authoritarian political settings, where civil society is relatively powerless, change cannot be achieved in ways that are contradictory and conflictual to the interests of a dominant regime. As such, incremental collaborative changes are more preferable and more effective than confrontational change options. The scope and extent of incremental changes would be larger the more collaborative is the civil society engagement.


: This study investigated the effect of speed management and ramp metering on traffic delay along arterials in Istanbul-Turkey. Urban arterial congestion is a recurring problem that affects urban traffic flow. Data were collected along 5·7 km long westbound approach arterial from the Anatolian side of Istanbul to the bridge initiated a study to investigate methods to mitigate congestion through traffic management and improved traffic flow. A micro simulation model based on traffic data using VISSIM software package suggested the applicability of traffic speed management along the existing infrastructure to relieve congestion and provide flow stability. Simulation was conducted along five hour which is the period of recorded data from 6:30 to 11:30 Am. The results indicated that the speed management could decreased traffic delay by an approximate 8% of delay from the existing value of 242 s/vehicle at 36 km/h to 202 s/vehicle at 65 km/h speed limits. Also, there were about of 17% increase in the total number of served vehicles from 23 844 vehicles/5 h to 28 244 vehicle/5 h. On the other hand, the optimum cycle time for ramp metering signal was 18 second. Applying of ramp metering strategy for 18 second cycle time led to 13,3% reduction in delay and 6.3 % increasing in flow speed. Finally, if ramp metering and speed management are applied together, the average delay is reduced to 188 seconds / vehicle from 242 s/vehicle ( reduction in average delay by 25% ). Also, average speed was increased by a 13% increase (from 36 to 41 km / h and).


CD4+ and CD8+ cytotoxic T‐cell (CTL) clones, selected for T‐ceII‐receptor (TcR)‐dependent lysis of the autologous tumor and isolated from peripheral‐blood lymphocytes (PBL) or tumor‐infiltrating lymphocytes (TIL) of 3 melanoma patients, were characterized for the pattern of 13 different cytokines released by antibody‐ or tumor‐mediated triggering. Induction or enhancement of cytokine release by anti‐CD3 monoclonal antibody (MAb) led to the identification of 2 major sub‐sets of CD8+ CTL clones on the basis of production of IL‐4. Within the 2 groups of IL‐4‐producing or non‐producing clones, further sub‐sets could be identified on the basts of differential production of IL‐1 p, IL‐2, IL‐6, IL‐8, IL‐10, TNF‐α, TNF β and IFN‐γ. A similar analysis performed on a panel of CD4+ CTL clones indicated multiple patterns consistent with at least 4 major sub‐sets, but further complexity was evident in each sub‐set on the basis of differential production of IL‐1, IL2, IL‐6, IL‐10 and G‐CSF. The cytokine profile of CD4+ and CD8+ clones, as determined after anti‐CD3 stimulation, was different from the pattern seen after co‐culture with autologous tumor, since many clones released cytokines such as IL‐4, IL‐10, IFN‐α and‐β, TNF‐γ and GM‐CSF after activation with only 1 of the 2 stimuli. These results indicate that CD4+ and CD8+ CTL clones reacting to human melanoma belong to a highly complex repertoire of functional subsets characterized by distinct cytokine profiles. In addition, the cytokine pattern of each T‐cell sub‐set can be modulated by changing the activation signals delivered to the T cell. © Wiley‐Liss, Inc.


Additive manufacturing (AM), also known as 3d printing, has become a hot topic in academia and industry in the past decades. For a typical layer-based additive manufacturing where the object is printed in a layer-by-layer fashion, the battle to reduce or even eradicate the support structure is always faced by researchers and industrial practitioners. The newly emerging multi-axis printing platform inspired by the five-axis machine tool opens new directions, such as surface quality improvement, support-free printing, etc. In this paper, we have presented a framework for the support-free hollowing of 3+2-axis printing. A suite of algorithms including curved skeleton extraction, print sequence optimization, hollowing generation, and print path planning is introduced. It is expected that the print efficiency will increase while the residue artifacts caused by the support structure on the contact surface can be ultimately eradicated.


OBJECTIVES
To investigate subclinical or clinical abnormalities in retinal and choroidal vascular plexuses in patients with systemic sclerosis (SSc) by means of optical coherence tomography angiography (OCT-A).

METHODS
A total of 20 consecutive SSc patients were recruited and compared to 20 healthy subjects. Quantitative analysis of vessel density (VD), choriocapillaris plexus flow index (CCP-FI) and choroidal vascularity index were performed on OCT-A images in the superficial capillary plexus (SCP), deep capillary plexus (DCP) and choriocapillaris for all patients. Images were further reviewed by two independent readers for the assessment of qualitative abnormalities, including tortuosity, rarefaction areas, megacapillaries and macular-foveal capillaries (MFC).

RESULTS
The DCP-VD in the whole scan and in parafoveal, superior, inferior, nasal and temporal regions was significantly lower in the SSc group. The CC-FI was significantly higher in SSc patients. When comparing SSc patients with and without digital ulcers (DUs), significantly reduced SCP-VD was demonstrated in the whole, parafoveal, superior, inferior, temporal and nasal regions. No difference in any of the OCT-A parameters was observed when comparing patients with or without interstitial lung disease (ILD). Qualitative analysis of OCT-A revealed at least one abnormality in 95% of patients.

CONCLUSIONS
We showed the ability of OCT-A to disclose early ocular vascular abnormalities in patients with SSc. Our results may represent a hypothesis-generating basis for exploring the potential role of OCT-A in diagnosis, monitoring and prognosis stratification in SSc.


Using the fact that 2D Newton constant is wholly induced by a conformal field theory, we derive a formula for the entanglement entropy of the anti-de Sitter black hole in two spacetime dimensions. The leading term in the large black hole mass expansion of our formula reproduces exactly the Bekenstein-Hawking entropy S_{BH}, whereas the subleading term behaves as ln S_{BH}. This subleading term has the universal form typical for the entanglement entropy of physical systems described by effective conformal fields theories (e.g. one-dimensional statistical models at the critical point).


Author(s): Naylor, Stephen Gordon | Advisor(s): Morgan, David O | Abstract: Post-translational phosphorylation of proteins by cyclin-dependent kinases (Cdks) enables regulation of cell cycle events with a temporal and spatial precision that would be unattainable by control of protein synthesis and degradation alone. To understand how processes are regulated to operate reliably in every repetition of the cycle thus requires an understanding of where and when Cdk-dependent phosphates appear throughout the proteome, and the molecular effects of those phosphates on the proteins in question.Cytokinesis, the process by which one cell divides and becomes two, involves the ordered assembly of several protein populations at the site of cell division. In the budding yeast Saccharomyces cerevisiae, this occurs at the bud neck and has the end result of coordinating the contraction of an actomyosin ring with the synthesis of the primary septum, a cell wall precursor. The assembly process occurs during a period or proteome-wide reversal of Cdk-dependent phosphorylation, and is known to be sensitive to perturbations of the Cdk regulatory system.This study focuses on Iqg1, an essential protein required for recruiting actin to the bud neck. Iqg1 is phosphorylated by Cdk1 (S. cerevisiae's sole essential Cdk) at several sites, and we find that mutation of these sites to yield a nonphosphorylatable Iqg1 disrupts the timing of several aspects of the pre-cytokinesis assembly process. When expressed in place of wild type Iqg1, the phosphomutant promotes early arrival of filamentous actin at the bud neck at levels comparable to those observed in response to global inhibition of Cdk1 activity. In this mutant, we also observe early onset of the accumulation of Iqg1 itself, and of Hof1, a regulator of primary septum deposition that we reveal as a likely Iqg1 in vivo binding partner.These results reveal a common point of regulation for the two processes that comprise cytokinesis and illuminate the relationships between proteins that govern the timing of assembly of a complex multi-protein apparatus. The quantitative fluorescence microscopy methods used also provide a system for the further study of the unique molecular consequences of phosphorylation for each of Cdk1's many protein substrates.


This article defines a general assignment problem a nd explains definition of a matching in a bipartite graph. This paper describes an assignment problem of tasks to resources in the transport company. This article contains the mathem atical allocation model of tasks, function optimization with constrains.


With respect to the public domain, the British North America Actof 1867 established a division of authority which is relatively simple in principle: residuary interest in property belongs to the Provinces while the Federal authority has no more than the power of exception. From this principle which is derived principally from article 109 of the 1867 Act, we can say that the Provinces have authority to legislate on questions affecting natural resources. However, the Canadian Parliament can also legislate on questions affecting natural resources. This is derived from either express authority granted it or from implied authority. In effect, the majority of the authority which permits the Canadian Parliament to legislate in matters affecting natural resources is derived either directly or indirectly from the application of its trenching power. The introductory clause of article 91 of the 1867 Act is an important source of the Federal authority over natural resources. Through the application of the national dimension theory, Ottawa has assumed control over atomic energy, off-store mineral resources, water management, and the expropriation of provincial lands. Moreover, through the application of emergency powers, Parliament could eventually legislate on a considerable number of subjects related to natural resources. Also, a number of the Federal Government's enumerated powers permit the control authority to legislate on questions of natural resources. The principle examples of this are its authority over the public debt and property, commerce, taxation, navigation, fisheries, Indians, the authority granted it by article 92(10c), and article 108 of the 1867 Act. One must thus conclude that by judicial interpretation, the Federal government has gained concurrent authority over natural resources through the application of the principle of Federal preponderance in case of conflict.


Record low austral winter rainfall totals over southwest Western Australia (SWWA) in 2010 saw a continuation of the multidecade‐long winter drought plaguing the region. During this season, the highest recorded positive Southern Annular Mode (SAM) value was measured, adding weight to an association of a positive SAM with anomalously low SWWA winter rainfall (SWR), and vice‐versa. However, such a SAM‐SWR teleconnection has been recently questioned. Using observational data in the post‐1979 satellite era, it is shown that such a SAM influence does exist. This coherence is confirmed with 1150 years of modelled 20th century SWR anomalies and SAM values from 23 climate models, showing that a nonlinear impact operates: the influence from a negative SAM is greater than that from a positive SAM. This explains why a small positive shift in the SAM can cause a large SWR reduction, as has been observed. A further test shows that models with a greater positive SAM trend systematically produce a greater future SWR reduction. As all climate models project an increase in the SAM these results suggest that as global warming continues unabated, SWWA winter droughts will be more persistent as atmospheric conditions become more unfavourable for drought‐breaking rains.


Environment Canada operated a thermodynamic profiling radiometer providing continuous temperature, humidity and liquid soundings during the Alpine Venue of the 2010 Winter Olympic Games. Retrievals were obtained in real time via neural networks and in post-processing via one-dimensional variational analysis (1DVAR). Background error covariance matrices for 1DVAR were calculated using brightness temperature from radiometer observations and from forward-modeled radiosonde and grid point model analysis. All radiometer, radiosonde and analysis data including all weather (rain, sleet and snow) conditions were included. 1DVAR retrieval errors, determined by comparison with radiosonde temperature and humidity soundings, are 1.6 C and 0.6 g/m 3 rms or less from the surface to 10 km height. This error is smaller than the representativeness error assigned to radiosonde data when they are assimilated into numerical weather models. These results suggest that 1DVAR retrievals are ready for operational use in numerical weather modeling and prediction.


We consider two fundamental stochastic optimization problems that arise in the context of supply-chain models, the single-period newsvendor problem and its multiperiod extension with independent demands. These problems are among the most well-studied stochastic optimization problems in the Operations Research literature. Most commonly, these problems are studied from the perspective that the input probability distributions are given in terms of specific probability distribution functions that are computationally tractable; under this assumption, both problems can be solved efficiently. Unfortunately, this information is unlikely to be available in practice, and hence we make the more realistic assumption that the probability distribution is given by a "black box" from which independent samples can be drawn. We give the first fully polynomial randomized approximation schemes for these two problems in this sampling-based model.Our work provides new insights into the power of two of the most often-used approaches to solving stochastic optimization problems, the sample average approximation (SAA) and stochastic dynamic programming. For the newsvendor problem, we show that by taking a polynomial number of samples and then solving the newsvendor problem with respect to the resulting approximation to the true distribution, we obtain provably near-optimal solution. This significantly extends the class of problems for which the SAA is known to yield a scheme. Finally, we show how to adapt the framework of stochastic dynamic programming to yield an approximation scheme for the multiperiod newsvendor problem with independent demands. We believe that this is an interesting first step towards the goal of providing a mechanism for deriving efficient approximate stochastic dynamic programming methods for a wide range of multistage stochastic optimization problems.


An accumulation of research results, laboratory and clinic, leads to revise the classification of disorders of anxious nature (anxiety disorders according to the DSM-III). An empirical confirmation allows to separate anxious states from panic attack and phobic behavior constituting a component separated from generalized anxiety, exaggerated emotional reactions to stress agents and obsessive-compulsive disorders. The response to pharmacotherapeutic agents and the important number of anxiety depression and mixed depression tends to make permeable the separating line between the nosological entities anxiety and depression. The observations of subjects suffering from endogenous anxiety obliges to revise the classification by introducing three varieties of neurotic anxiety: phobic endogenous anxiety, endogenous anxiety without phobic formation, and exogenous anxiety. Endogenous anxiety is close to the concept of anxious thymopathy. By its pragmatic conception, modifications obtained by psychoactive agents are used (antidepressants of the group imipramine and IMAO, classical benzodiazepines and alprazolam, provocation controlled in laboratory) in order to strengthen innovating hypotheses and allow to elaborate useful treatment strategies for neuroses.


Abstract Hydropower reservoirs impounded by high-head dams exhibit complex circulation that confuses the downstream migrating salmon and limits successful collection and passage of fish. Fish passage engineers attempt to modify the hydrothermal behavior at reservoirs through structural and operational modifications and often use hydrodynamic simulations to guide their actions. Simulation of key hydrothermal processes such as (a) development of a stable two-layer stratified system, (b) density-driven currents over a reservoir length scale, and (c) discharge hydraulics near the power generation and fish collection intakes requires highly specialized models applied at differing temporal and spatial scales. A staged modeling approach is presented that uses external coupling of models at varying temporal scales and spatial resolution to simulate the entire hydraulic regime from the mouth of the reservoir at the upstream end to the discharge at the dam. The staged modeling approach is illustrated using a case study where structural modifications were evaluated to improve reservoir stratification and density-driven currents. The model results provided input and valuable insight in the development of a new structure design and configuration for effective fish collection near the forebay of a high-head dam.


After years of heavyweight software process models there is a trend in industry towards agile methods for the development of business information systems. Experience shows that these approaches are promising, but there is still the demand for a lean and practicable, yet predictable approach for developing business information systems.

With our approach we present the essence of experience in the area of business information systems development, which has been enriched with current scientific trends and findings to finally provide a practicable and useful approach.

This approach, called No-Frills Software Engineering, is based on principles which address artifact quality and value orientation. These principles guide the socalled main activities during the actual software development. In this paper we motivate our approach and explain its core principles and main activities.


Corneille, Huart, Becquart, & Brédart (2004) found that people remember ambiguous race faces as closer to a race prototype than they actually are. In three studies, we examined whether this memory bias generalizes to voice memory. In Studies 1 and 2, participants listened to synthesized male and female speech samples (high, moderate, or low pitch) and were asked to identify a voice target when paired against distracters higher or lower in pitch. The results showed that pitch distortions occurred, with the pattern consistent with assimilation toward low and high ends of the pitch continuum. Study 3 replicated this result with a wider voice pitch range. The results parallel those of Corneille et al. (2004). The implications of this work are discussed.


Abstract. Lestari P, Utami NW, Wawo AH. 2019. Adaptation on low light intensity of lesser yam (Dioscorea esculenta) under artificial shading. Pros Sem Nas Masy Biodiv Indon 5: 374-382. Tubers can be used as an alternative food to reduce dependence on rice. Current status of lesser yam is considered rare. However, it can still be found in people's yards in some areas of Java island, especially the older generation. The high content of inulin in the lesser yam tuber makes it feasible to be one candidate potential functional food source. The planting of lesser yam in the agroforestry component has important meaning to increase the productivity of the alleyway between forest crop and ex situ lesser yam conservation. The introduction of low-input lowland cultivation can be a factor to attract the farmer to cultivate lesser yam. The experiments were prepared based on the RCBD nested design. The research is intended as a baseline data to determine the adaptation of lesser yam to low light intensity stress. The data can be applied to determine the age of main timber plant commodities that can still be interspersed with lesser yam. The study was conducted with nesting plots. The level of shade as the main plot consists of 0% shade, 25% shade, 55% and 75% shades. Organic fertilizer as a subplot consists of no fertilizer and with fertilizer. Each treatment having 3 replications consisting of 3 plant observations. Organic fertilizer gave since 2 weeks after planting with a dose of 25cc / lt every week until the plant is 3 months old. Observations were made in plant growth, yield, and physiological phases. Almost all observation variables showed shade treatment more affecting growth and production of crops than fertilizer treatment. This good growth shows that the canopy of the plant grows optimally in full light conditions. Under different shade conditions, total yields did not differ between shade levels up to 50%, but tuber production was more uniform in shade 25% and 50%. Further research is needed on the interaction of lesser yam in various timber commodities as a major component of agroforestry.


Four sea snakes (two Hydrophis major, one Hydrophis platurus, one Hydrophis elegans) were found washed ashore on different beaches in the Sunshine Coast region and Fraser Island in Queensland, Australia between 2007–2013. Each snake had multiple granulomas and locally extensive regions of pallor evident in the hypaxial and intercostal musculature along the body. Lesions in two individuals were also associated with vertebral and rib fractures. Histological examination revealed granulomas scattered throughout skeletal muscle, subcutaneous adipose tissue and fractured bone. These were composed of dense aggregates of microsporidian spores surrounded by a mantle of macrophages. Sequences (ssrRNA) were obtained from lesions in three sea snakes and all revealed 99% similarity with Heterosporis anguillarum from the Japanese eel (Anguillarum japonica). However, ultrastructural characteristics of the organism were not consistent with those of previous descriptions. Electron microscopic examination of skeletal muscle revealed large cysts (not xenomas) bound by walls of fibrillar material (Heterosporis-like sporophorocyst walls were not detected). The cysts contained numerous mature microsporidian spores arranged in small clusters, sometimes apparently within sporophorous vesicles. The microspores were monomorphic, oval and measured 2.5–3.0 μm by 1.6–1.8 μm. They contained isofilar polar filaments with 11 (infrequently 9–12) coils arranged in two ranks. This is the first published report of a microsporidian infection in hydrophiid sea snakes. This discovery shows microsporidia with molecular affinities to Heterosporis anguillarum but ultrastructural characters most consistent with the genus Pleistophora (but no hitherto described species). Further studies are required to determine whether the microsporidian presented here belongs to the genus Heterosporis, or to a polymorphic species group as suggested by the recognition of a robust Pleistophora/Heterosporis clade by molecular studies. The gross and histological pathology associated with these infections are described.


Pilomatrical carcinosarcoma is a very rare entity, with only six cases reported until now. This report describes the case of a 100‐year‐old woman with a mass on the left temple that had existed for several decades but had recently grown in size. Histology showed an asymmetric lesion composed of basaloid cells, spindle cells, and "shadow" or "ghost" cells. Cells had atypical hyperchromatic nuclei with prominent nucleoli, high mitotic activity, and atypical mitosis. In the central area, an epidermal cyst‐like structure was seen. The diagnosis of pilomatrical carcinosarcoma was rendered. This case appeared to have arisen from malignant transformation of a pilomatricoma because of the long clinical history and existence of a benign epidermal cyst‐like structure. In addition, the observation that the basaloid cells and spindle cells showed a gradual transition from one to the other and that both types were positive for β‐catenin would seem to support a common clonal origin for the carcinomatous and sarcomatous components.


We have designed, constructed, and tested an x-ray laser resonator operating in the hard x-ray, keV energy region. This ring x-ray laser cavity is formed by four highly oriented pyrolytic graphite crystals. The crystals are set at the Bragg angles that allow for the complete 360° round trip of the 2.37 A, 5.23 keV Lα line of neodymium. In addition, we also present experimental data of a similar ring laser resonator that utilizes the Cr Kα, 5.41 keV, x-ray line to propagate through the four mirrors of the cavity. The specific properties of these x-ray laser resonator mirrors, including reflection losses and cavity arrangement, are presented.


Calcium ion decreases the motional freedom of lipid molecules in isolated rat hepatocyte plasma membranes and in sonicated dispersions (liposomes) of the membrane lipid. The decrease in lipid fluidity was monitored by estimation of the fluorescence polarization of 1,6-diphenyl-1,3,5-hexatriene. At least two processes are involved in the mode of action of the cation. The first is direct, i.e., observed on addition of calcium to the liposomes, relatively rapid, with a half-time of 10-15 at 37 degrees C, proportional to the calcium concentration in the range 0-4 mM, and readily reversed on addition of excess EDTA. The second mechanism is indirected and requires the presence of the membrane proteins. It occurs relatively slowly, with a half-time of 75 min at 37 degrees C, tends to plateau with a calcium half-saturation concentration of approximately 1 mM, is of greater magnitude than the direct effect, and cannot be reversed on chelation of calcium by EDTA. Moreover, the indirect effect is specific for Ca2+ as compared to other divalent cations and it results in changes in the lipid composition. Stimulation of phospholipase A activity is likely but does not account for the change in fluidity. The direct action of calcium is ascribed to binding to the lipid bilayer, whereas the indirect action probably results from modulation of membrane-bound enzymes which can alter the lipid composition. The effects of calcium on the membrane lipid fluidity may underly certain of its regulatory actions on membrane functions.


The incidence of thrombo-embolic complications in pregnancy varies between 2 and 5 per 1000 deliveries. Deep-vein thrombosis (DVT) is classically associated with pulmonary embolism and chronic venous insufficiency, which are leading causes of maternal morbidity and mortality. An accurate diagnosis of iliofemoral or calf vein thrombosis should be confirmed by either Doppler ultrasonography, impedance plethysmography or ascending phlebography. Full-dose continuous intravenous heparin for 5-10 days is the established method of therapy for acute DVT and pulmonary embolism occurring during pregnancy or in the puerperium. Thereafter, long-term treatment with self-administered subcutaneous injections of heparin in low doses is feasible and effective. During pregnancy, coumarin administration results in embryopathy as it readily crosses the placenta; it should be avoided until after delivery. In view of its safety and effectiveness, low-dosage intravenous heparin or heparin by subcutaneous injection seems to be the anticoagulant of choice for the expectant mother.


Osteoma cutis describes bone formation in skin and is well documented in the medical literature, but veterinary reports are few. We report a single case of a juvenile samoyed that was referred for assessment of a superior eyelid anomaly. Exploratory surgery and histopathology revealed the presence of mature, lamellar bone within the superior eyelid. The histologic appearance was consistent with primary osteoma cutis. The presence of the ossification within the deep dermis of the eyelid was associated with an abnormal conformation causing trichiasis, keratitis and dorsal strabismus. Identification of the osseous lesion during surgery and its removal was curative with no recurrence of disease during the 32 month follow-up period.


A coupling between a light scalar field and neutrinos has been widely discussed as a mechanism for linking (time varying) neutrino masses and the present energy density and equation of state of dark energy. However, it has been pointed out that the viability of this scenario in the non-relativistic neutrino regime is threatened by the strong growth of hydrodynamic perturbations associated with a negative adiabatic sound speed squared. In this paper we revisit the stability issue in the framework of linear perturbation theory in a model independent way. The criterion for the stability of a model is translated into a constraint on the scalar-neutrino coupling, which depends on the ratio of the energy densities in neutrinos and cold dark matter. We illustrate our results by providing meaningful examples both for stable and unstable models. PACS numbers: 13.15.+g, 64.30.+t, 64.70.Fx, 98.80.Cq Neutrino Dark Energy – Revisiting the Stability Issue 2


Abstract Mammals can influence growth, reproduction, competitive ability, and survival of woody plants by virtue of selective browsing and gnawing of dormant shoots during winter. Apparently in response to this type of herbivory, plants have evolved chemical and mechanical deterrents to mammalian herbivores. We report on plant ontogeny and biogeography, which exert their influence on herbivory at different spatiotemporal scales. To evaluate how plant ontogeny influences herbivory, we conducted a meta-analysis of 128 studies, encompassing 37 plant and 10 mammal species, in which juvenile and mature growth stages of conspecific plants were made available to mammals during winter in temperate and northern latitudes. Mammals ate more of the mature-stage growth in 96% of the studies, and stage-specific differences in consumption were very large (d+ = 2.16). Plants characterized by rapid growth rates or low tolerances to resource limitation elicited the greatest degree of stage-specific discrimination by mammals, consistent with existing theories regarding tradeoffs governing plant growth and defense. The influence of a plant's growth rate and tolerance to resource limitation was dependent on climatic regime; plants grown in areas with harsh winter conditions tended to elicit greater discrimination of juvenile- and mature-stage growth by mammals than plants grown in more moderate climates. Further evidence for biogeographical variation in mammalian consumption came from 14 feeding studies, including 6 plant and 6 mammal species, that compared conspecific plants of the juvenile growth stage either grown or collected at different localities. In 86% of the studies, extent of herbivory by mammals varied inversely with latitude, and this yielded a moderate effect (Z+ = −0.46, r+ = −0.53). We discuss potential roles of life history, climate, and historical association of plants and mammals in shaping these biogeographical patterns.


Background Accumulation of DNA damage leading to adult stem cell exhaustion has been proposed to be a principal mechanism of aging. Here we tested this hypothesis in healthy individuals of different ages by examining unrepaired DNA double-strand breaks (DSBs) in hematopoietic stem/progenitor cells matured in their physiological microenvironment. Methodology/Principal Findings To asses DNA damage accumulation and repair capacities, γH2AX-foci were examined before and after exposure to ionizing irradiation. Analyzing CD34+ and CD34− stem/progenitor cells we observed an increase of endogenous γH2AX-foci levels with advancing donor age, associated with an age-related decline in telomere length. Using combined immunofluorescence and telomere-fluorescence in-situ hybridization we show that γH2AX-foci co-localize consistently with other repair factors such as pATM, MDC1 and 53BP1, but not significantly with telomeres, strongly supporting the telomere-independent origin for the majority of foci. The highest inter-individual variations for non-telomeric DNA damage were observed in middle-aged donors, whereas the individual DSB repair capacity appears to determine the extent of DNA damage accrual. However, analyzing different stem/progenitor subpopulations obtained from healthy elderly (>70 years), we observed an only modest increase in DNA damage accrual, most pronounced in the primitive CD34+CD38−-enriched subfraction, but sustained DNA repair efficiencies, suggesting that healthy lifestyle may slow down the natural aging process. Conclusions/Significance Based on these findings we conclude that age-related non-telomeric DNA damage accrual accompanies physiological stem cell aging in humans. Moreover, aging may alter the functional capacity of human stem cells to repair DSBs, thereby deteriorating an important genome protection mechanism leading to exceeding DNA damage accumulation. However, the great inter-individual variations in middle-aged individuals suggest that additional cell-intrinsic mechanisms and/or extrinsic factors contribute to the age-associated DNA damage accumulation.


Synchronization of two actuated sheets serves as a simple model for the interaction between flagellated microswimmers. Various factors, including inertia, sheet elasticity, and fluid viscoelasticity, have been suggested to facilitate the synchronization of two sheets; however, the importance of different contributions to this process still remains unclear. We perform a systematic investigation of competing effects of inertia, sheet elasticity, and fluid viscoelasticity on the synchronization of two sheets. Characteristic time $\tau^\mathrm{s}$ for the synchronization caused by inertial effects is inversely proportional to sheet Reynolds number $\mathrm{Re}$, such that $\tau^\mathrm{s} \omega \propto \mathrm{Re}^{-1}$ with $\omega$ being the wave frequency. Synchronization toward stable in-phase or opposite-phase configuration of two sheets is determined by the competition of inertial effects, sheet elasticity, fluid compressibility and viscoelasticity. Interestingly, fluid viscoelasticity results in strong synchronization forces for large beating amplitudes and Deborah numbers $\mathrm{De} > 1$, which dominates over other factors and favors the in-phase configuration. Therefore, our results show that fluid viscoelasticity can dramatically enhance synchronization of microswimmers. Our investigation deciphers the importance of different competing effects for the synchronization of two actuated sheets, leading to a better understanding of interactions between microswimmers and their collective behavior.


In this letter, we present an efficient algorithm for the removal of random-valued impulse noise from a corrupted image by using a reference image. The proposed method uses a statistic of rank-ordered relative differences to identify pixels which are likely to be corrupted by impulse noise. Once a noisy pixel is identified, its value is restored by a simple weighted mean filter. Simulation results indicate that our algorithm provides a significant improvement over many other existing techniques.


CD90 has been identified as a marker for liver cancer stem cells (CSCs) that are responsible for tumorigenic activity, but it is not known how CD90+ cells contribute to tumor initiation and progression. Our data demonstrated that high expression of CD90 in Hepatocellular Carcinoma (HCC) tissues correlated with venous filtration in HCC patients. CD90+ cells isolated from HCC cell lines exhibited increased tumorigenicity, chemoresistance, tumor invasion and metastasis. Notch pathway was activated in CD90+ cells and we found that inhibition of Notch pathway in CD90+ CSCs decreased tumorigenicity, cell invasion, migration and expression of stem cell related genes. Activation of Notch pathway in CD90− cells induced self-renewal, invasion and migration. Furthermore, we observed that cancer stem cell features were facilitated by stimulating G1-S transition in the cell cycle phase and inhibiting apoptosis mediated by Notch pathway. Our findings suggested CD90 could be used as a potential biomarker for HCC CSCs, and that cancer stem cell activity was elevated through up activated Notch pathway in CD90+ CSCs.


Multifunction Vehicle Bus (MVB) is a highly robust real-time field bus for rail vehicles. On MVB, periodic process data and sporadic message data are transmitted in the form of telegrams. The main focus of this paper is the development of heuristic scheduling algorithms for periodic telegrams on MVB. We first propose two heuristics that find the best location of individual telegrams in the MVB schedule based on different criteria. Then, we introduce a new swap operation that allows improving MVB schedules by exchanging the locations of telegrams. A comprehensive evaluation based on a large number of test cases shows that the proposed heuristics are able to find feasible and close-to-optimal MVB schedules with practical computation times. In particular, our heuristics clearly outperform an existing ILP formulation, that cannot find optimal or even feasible schedules in cases with large telegram sets.


A review of the experimental study of single-mode oscillators based on stimulated bremsstrahlung and Cerenkov radiation of high-current relativistic electron beams is given. Three types of Cerenkov oscillators are investigated in detail: orotrons, surface wave oscillators and a flimatron (free electron maser (FEM) based on Smith-Purcell radiation). The bremsstrahlung oscillators studied are gyrotrons with TM modes, a ubitron operating at a quasi-critical frequency and cyclotron autoresonance masers. Electrodynamic and electron methods of mode selection provide stable radiation with a reproducible space structure of radiation in all oscillators under study. The radiation power attained 50-100 MW for long and 10-30 MW for short millimeter wavelengths at the efficiency up to 5-10 percent. Various types of oscillators are compared. Promising methods for increasing power and radiation frequency are discussed.


Interrelationships of immunologic and enzymatic markers of histiocytes have been studied in malignant neoplasms of histiocytic/monocytic origin and in differential diagnostically relevant, large cell non‐Hodgkin's lymphomas. Cryostat sections required for demonstrating cell surface antigens by monoclonal antibodies are inadequate for studying cellular detail, enzymatic maturation by alpha‐naphthyl acetate esterase (ANAE), and demonstrating the classical cytoplasmic markers of histiocytes like lysozyme, alpha‐1‐antitrypsin (AT), and alpha‐1‐antichymotrypsin (ACT). These markers have been compared in gently fixed and vacuum paraffin‐embedded material. The reactivity for monoclonal anti‐human monocyte 1 (Mo 1) has also been preserved by this method. Malignant histiocytosis (MH) is characterized by a heterogeneous cell population. The mature, ANAE‐positive cells with macrophage morphology usually show a diffuse cytoplasmic positivity for AT and ACT. Lysozyme is moderately positive to negative in these cells, but it is more efficient than these markers in revealing smaller cells resembling monocytes by focal positivity in the cytoplasm. The expression of Factor XIIIa (F‐XIIIa) is connected with the phagocytic activation of histiocytic cells. F‐XIIIa positive cells usually form a minority of the neoplastic population in MH, but the large cytophagocytic marcophages are invariably positive. Reactive macrophages in large cell non‐Hodgkin's lymphomas are characterized by a coexpression of ANAE, AT, ACT, lysozyme, F‐XIIIa and Mo 1. Typical cases of true histiocytic lymphoma (THL) are made up of a homogeneous population showing the above mature, phagocytizing phenotype. in MH, Mo 1 and ANAE recognize different subpopulations. The reciprocal relation of these markers is an abnormal phenotypic feature. The results presented in this article prove the diagnostic value of ANAE and lysozyme in confirming the histiocytic differentiation of malignant cells. Monoclonal anti‐human monocyte 1 is useful for identifying the immature component in MH. Factor XIIIa can be considered a functional marker of mature phagocytic histiocytes and an aid in the diagnosis of THL.


The optimal traverse of irregular terrains made by ground mobile robots heavily depends on the adequacy of the cost models used to plan the path they follow. The criteria to define optimality may be based on minimizing energy consumption and/or preserving the robot stability. This entails the proper assessment of anisotropy to account for the robot driving on top of slopes with different directions. To fulfill this demand, this paper presents the Continuous Anisotropic Model for Inclined Surfaces, a cost model compatible with anisotropic path planners like the bi-directional Ordered Upwind Method. This model acknowledges how the orientation of the robot with respect to any slope determines its energetic cost, considering the action of gravity and terramechanic effects such as the slippage. Moreover, the proposed model can be tuned to define a trade-off between energy minimization and Roll angle reduction. The results from two simulation tests demonstrate how, to find the optimal path in scenarios containing slopes, in certain situations the use of this model can be more advantageous than relying on isotropic cost functions. Finally, the outcome of a field experiment involving a skid-steering robot that drives on top of a real slope is also discussed.


In the present work, different kinds of porous copolymer networks based on 2-vinylpyridine (2VP) and divinylbenzene (DVB) containing anchored iodine were prepared and evaluated for inactivating Escherichia coli in an aqueous medium. By using bacterial viability assays with E. coli (AB 1157, wild-type), the iodine bactericidal effect was investigated at room temperature by elution through short columns filled with copolymer beads. Saline solutions containing bacterial cells at several contents (102 to 107 cells/mL) were eluted. After each elution, cell content viability was determined by plating these suspensions on nutritive agar plates, incubating them at 37°C for 24 h, and counting as colony-forming units (CFUs). It was verified that the networks containing anchored iodine were completely bactericidal within a few minutes. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 93: 972–976, 2004


Mesenteric cysts are rare, benign gastrointestinal cystic lesions, which are often non-troublesome and present as an incidental radiological finding. However, surgery is often performed in the acute setting to remove lesions that are symptomatic. This report highlights the case of a large, symptomatic mesenteric cyst managed successfully with initial conservative measures followed by planned elective surgery. A 44-year-old female presented with a four-day history of generalised abdominal pain associated with distension, fever, diarrhoea and vomiting. Computer tomography revealed a large (21.7 cm × 11.8 cm × 14 cm) mesenteric cyst within the left abdomen cavity. She was admitted and treated conservatively with intravenous fluids and antibiotics for four days, which lead to complete symptom resolution. Follow-up at intervals of one and three months revealed no return of symptoms. An elective laparotomy and excision of the mesenteric cyst was then scheduled and performed safely at nine months after the initial presentation. Compared to acute surgery, acute conservative management followed by planned elective resection of a symptomatic mesenteric cyst may prove safer. The withholding of an immediate operation may potentially avoid unnecessary operative risk and should be considered in patients without obstructive and peritonitic symptoms. Our case demonstrated the safe use of initial conservative management followed by planned elective surgery of a mesenteric cyst found in the acute setting, which was symptomatic but was not obstructive or causing peritonitic symptoms.


Increased levels of reactive oxygen species attributed to oxidative stress have been found to be responsible for the development of some vital diseases such as cardiovascular, neurodegenerative and autoimmune diseases. Recently, it was observed that melatonin is a highly important antioxidant, and melatonin analogues are under investigation to find out improved antioxidant activity. In this study, 14 melatonin ‐based analogue indole amino acid and N‐protected amino acid derivatives were synthesized and elucidated spectrometrically. To investigate the antioxidant activity of the synthesized compounds and to compare with melatonin, butylhydroxytoluene and vitamin E, lipid peroxidation inhibition and 2,2‐diphenyl‐1‐picrylhydrazyl radical‐scavenging activities were tested. The results indicated that the synthesized new indole amino acid derivatives have similar activities to melatonin in 2,2‐diphenyl‐1‐picrylhydrazyl radical‐scavenging activity assay but more potent activities in lipid peroxidation inhibition assay.


OBJECTIVES
To elucidate the longitudinal reciprocal association between rheumatoid arthritis (RA) and chronic obstructive pulmonary disease (COPD), and the mediating role of systemic inflammation in the association.

METHODS
403045 participants from UK Biobank were enrolled in this study. A cross-lagged panel model was used to investigate the longitudinal reciprocal association between RA and COPD. Cox-proportional hazard regression and logistic regression models were also conducted to examine the association between baseline RA and COPD during follow-up, and vice versa. Causal mediation analysis was then performed to explore the mediating roles of 160 systemic inflammatory biomarkers in the bidirectional association.

RESULTS
At baseline, 4755 (1.2%) and 6989 (1.7%) individuals were diagnosed with RA and COPD, respectively. After adjusting for the covariates, the result of cross-lagged panel model revealed a bidirectional association between RA and COPD (β  =  0.018, P < 0.001 for RA→COPD path; β  =  0.010, P < 0.001 for COPD→RA path). In the non-COPD population, the risk of future COPD was increased in RA patients (Cox: HR = 1.65, 95% CI, 1.50-1.83; logistic: OR = 1.85, 95% CI, 1.66-2.07). In the non-RA population, baseline COPD was associated with a higher risk of RA during follow-up (Cox: HR = 1.67, 95% CI, 1.44-1.92; logistic: OR = 1.70, 95% CI, 1.47-1.97). Five inflammatory factors mediated the RA→COPD path, and C-reactive protein mediated the COPD→RA path (FDR < 0.05).

CONCLUSIONS
A significant bidirectional association exists between RA and COPD, and it is partially mediated by systemic inflammation.


The expression of critical exponents in wetting transition at two-phase and three-phase coex-istence in Sullivan mixture are studied, It is found that the critical exponents depend neither on the model parameters not on the symmetry of dynamical potential, i. e.: the exponents have universality.


An analytic hybrid method is considered for solving the stationary radiation transfer equation in the problem on reflection of a narrow laser beam from biological media such as the 2% aqueous solution of intralipid and erythrocyte suspension with the volume concentration (hematocrit) H=0.41. The method is based on the reciprocity of the Green function in the radiation transfer theory and on the iteration solution of the integral equation for this function. As a result, the ray intensity is represented as a sum of two terms. The first of them describes the contribution of finite-order scattering to the intensity of a beam diffusely reflected from the medium. The second term contains the explicit analytic expression for a spatially distributed effective source of diffuse radiation emerging from the deep layers of the medium to the surface. This approach substantially improves the diffusion approximation for the problem under study and allows one to obtain the uniform asymptotics of the reflection coefficient at the specified interval of distances between the radiation source and detector on the medium surface with the relative error within ±6% for the 2% intralipid emulsion and erythrocyte suspension (H=0.41).


To define an Arabic poet and his style as individualistic is highly problematic. From the beginning Arabic poetry was extremely conventional. Most themes in early Bedouin poetry were well established and primarily focused on love and the desert. While the desert motifs remained in later Arabian poetry, new urban themes such as drinking scenes and the poet's longing for the young female or male servant who poured the wine came into vogue. The paper looks at Ibn Khafāja's poetry, its poetic form and how the poet's individualistic use of stock motifs gives his oeuvre a unique character.


The increasing use of parallel/distributed applications demands a continuous support to take significant advantages from parallel power. This includes the evolution of performance analysis and tuning tools which automatically allows for obtaining a better behavior of the applications. Different approaches and tools have been proposed and they are continuously evolving to cover the requirements and expectations of users. One such tool is MATE (Monitoring Analysis and Tuning Environment), which provides automatic and dynamic tuning for parallel/distributed applications. The knowledge used by MATE to analyze and take decisions is based on performance models which include a set of performance parameters and a set of mathematical expressions modeling the solution of the performance problem. These elements are used by the tuning environment to conduct the monitoring and analysis steps, respectively. The tuning phase depends on the results of the performance analysis. This paper presents a methodology to specify performance models. Each performance model specification can be automatically and transparently translated into a piece of software code encapsulating the knowledge to be straightforwardly included in MATE. Applying this methodology, the user does not have to be involved in the implementation details of MATE, which makes the usage of the tool more transparent. Copyright © 2011 John Wiley & Sons, Ltd.


In biological systems, chemical signals termed morphogens self-organise into patterns that are vital for many physiological processes. As observed by Turing in 1952, these patterns are in a state of continual development, and are usually transitioning from one pattern into another. How do cells robustly decode these spatio-temporal patterns into signals in the presence of confounding effects caused by unpredictable or heterogeneous environments? Here, we answer this question by developing a general theory of pattern formation in spatio-temporal variations of 'pre-pattern' morphogens, which determine gene-regulatory network parameters. Through mathematical analysis, we identify universal dynamical regimes that apply to wide classes of biological systems. We apply our theory to two paradigmatic pattern-forming systems, and predict that they are robust with respect to non-physiological morphogen variations. More broadly, our theoretical framework provides a general approach to classify the emergent dynamics of pattern-forming systems based on how the bifurcations in their governing equations are traversed.


Traumas to the mandible in children, due to falls or traffic accidents, can involve fractures in the condylar area. Without timely and proper diagnosis, such fractures may give rise to serious problems, such as growth disturbances of the face and disorders of the temporomandibular joint. Orthodontists are often involved in the diagnosis of condylar fractures but, more importantly, they should be involved in the successful conservative management of the fracture. The aim of this article is to present 5 cases of isolated condylar fractures in children (2 boys, 3 girls; age range 4.5 to 10 years) who were diagnosed and treated solely by a conservative orthopedic approach, involving the use of a functional appliance (activator). After a follow-up period of 1 year, clinical and radiologic examination indicated, due to the growth potential of the condyles during childhood, successful healing and remodeling had occurred in all 5 cases and no discomfort or complications were reported. A conservative treatment approach for an isolated condylar fracture, using a functional appliance during the growth period, can lead to complete restoration of the fractured area and re-establishment of physiologic function of the stomatognathic system with no signs of disturbance in dentofacial development.


We show that ex ante identical oligopolists may find it optimal to contribute asymmetrically to a research joint venture. The reason is found in the trade-off between the desire to increase the variance of the distribution of unit costs within the oligopoly (which increases gross profit, though not necessarily net profit, of the group) and the incentive to efficiently carry out R&D activities by equalizing marginal R&D costs across firms. Conditions for non-existence of symmetric contributions are given. We also propose a profit sharing rule for asymmetric research joint ventures.

JEL Classification Numbers: L13, L23.


Background We have little knowledge of reference values for acetabular angles. Purpose The purpose of this study was to report values and variation for the center-edge (CE), the acetabular-index (AI), the anterior-sector (AASA), the posterior-sector (PASA), and the acetabular-anteversion angle (AcAV) and to investigate gender differences. Material and Methods Retrospectively, we recruited 96 individuals, 52 women (mean age = 63 ± 12 years) who had undergone computed tomography (CT) as part of examination for lymphomas in 2013 at Aarhus University Hospital. After CT, the participants completed the Oxford Hip Score. Eight individuals indicated hip problems and three had missing data; those 11 were excluded from the material. The acetabular angles for both hips were measured on CT images by an experienced radiologist. The acetabular angles are reported for right and left hip as mean ± SD degrees and compared women and men with a two-sample t-test. Results The CE angle [right;left] averaged [34±6;35±5]. The AI angle averaged [3±6;1±5]. The AASA averaged [58±7;60±9]. The PASA averaged [94±7;95±7]. The AcAV averaged [18±5;18±5]. The AASA was lower whereas the PASA and the ACAV were higher for women compared to men. Conclusion We found considerable variation in the values for acetabular angles. There were gender differences in the sector angles and for the AcAV. Knowledge of reference values is important when we attempt to diagnose the pathological hip conditions.


Background:Phaseolus vulgaris commonly known as kidney bean has been studied previously for pharmacological activities like antidiabetic, antioxidant, analgesic, anti-inflammatory, antifungal and antibacterial properties. Various extracts of the seeds have been researched except fixed oils.
Objective: Therefore objective of the present study is to investigate the behavioural activity of fixed oil extracted from Phaseolus vulgaris seeds.
Methodology: Hole board, light and dark , stationary rod and open field tests were used for behavioral evaluation. Four groups were made with seven mice in each :  (1) Control = Normal saline 2ml/kg (2) Phaseolus vulgaris fixed oil = PVFO 2ml/kg (3)  PVFO 4ml/kg (4) Diazepam (1mg/kg) as standard. All treatments were given orally, 30 minutes prior to the performance of tests. In hole board test PVFO 4ml/kg decreased the number of head poking (p≤0.01).
Results:In light and dark test PVFO in both doses decreased the time spent in light compartment (p≤0.01). In open field test number of peripheral lines crossed were decreased (p≤0.05) whereas in stationary rod test no effect was observed by any dose of PVFO.
Conclusion:Results indicate that Phaseolus vulgaris  fixed oil does not affect memory or learning in mice and may possess a dose dependent sedative hypnotic effect


The picked pear is often ripened naturally or artificially in ethylene solution to put the pear into market earlier.When Qiuxiang pear are ripened,a great deal of ethylene is produced,the content of soluble solid,total sugar and titrable acidity are increased.The flesh is softened,the skin of fruit turns yellow,and the fruits are of aromatic favor.At different harvest time,respiration intensity appears different changing trends;the fruit qualities and the storage period are influenced too.Artificial ripening promotes fruit ripe and has a better effect than natural ripening.And Qiuxiang pear ripened artificially in earlier the middle or late of August can achieve better fruit qualities and higher economic value.


Can the Terms of Policies of social media platforms be made more comprehensible, transparent, and consumer-friendly? Dreyer and Ziebarth suggest that "participatory transparency," based in the community of users, can help overcome contractual complexity and legal jargon while increasing user awareness. They recommend the use of autonomous bodies of third-party users to crowd-source platform-specific suggestions for improvements, and to translate terms and provisions into practical pointers. Implementation may be slow because platform providers may resist this approach, but the authors argue that the process has many benefits for the providers as well.


ABSTRACT In the first year of the journal of Legal Pluralism's existence, Keebet von Benda-Beckmann's article Forum shopping and shopping forums. Dispute processing in a Minangkabau village in West Sumatra was published. Christian Lund reflects on the continued theoretical and methodological relevance of the article for the social scientific study of law and legal pluralism, property and conflict, institutions and authorities, and the role of claimants.


This is a report of the 'TCEC Cup 1' computational experiment, the first TCEC knockout event and the second major part of TCEC's 13th season. It featured the best 32 engines of 'TCEC 13' and the games were held at Blitz tempo, The different format called for different optimal settings in the engines, thereby enabling a comparison with performance at slower tempi. This event notably featured the first appearance of two non-Shannon-AB, neural-network/MCTS engines, DEUS X and LEELA CHESS ZERO. LC0 notably was a quarter-finalist, having started as 21st seed. STOCKFISH beat HOUDINI in the final with the sole win, remarkably, a short and dramatic game. All decisive games in the supplementary data have been played out by FRITZ17 at search depth 24 to benchmark endgame practice.


Financial constraints in health care in general and critical care services in particular have placed increasing demands upon health care professionals and decision-makers to ensure the highest quality of care with the best possible outcomes are attained for the least possible expenditure of resources. As such, pharmacoeconomic methods have become increasingly applied to pressing clinical problems to facilitate cost-effective delivery of health care services to the critically ill. This manuscript briefly details the basic tenets of pharmaco-economic analysis and provides an overview of recent applications to critical care issues.


A new type of carbon nanotube, based on the graphenylene motif, is investigated using density functional and tight-binding methods. Analogous to conventional graphene-based nanotubes, a two-dimensional graphenylene sheet can be "rolled" into a seamless cylinder in armchair, zigzag, or chiral orientations. The resulting nanotube can be described using the familiar (n,m) nomenclature and possesses 4-, 6-, and 12-membered rings, with three distinct bond lengths, indicating a nonuniform distribution of the electron density. The dodecagonal rings form pores, 3.3 Å in diameter in graphenylene, which become saddle-shaped paraboloids in smaller-diameter nanotubes. Density functional theory predicts zigzag nanotubes to be small-band gap semiconductors, with a generally decreasing band gap as the diameter increases. Interestingly, the calculations predict metallic characteristics for armchair nanotubes with small diameters (<2 nm), and small-band gap semiconducting characteristics for larger-diameter ones. Graphenylene nanotubes with indices mod(n-m,3) = 0 exhibit a band gap approximately equal to that of armchair graphenylene nanotubes with comparable diameter.


In this paper we explore how specific individual and group characteristics may influence students' contribution in a collaborative task as well as their progress after collaboration. An empirical study is described, where students worked on concept mapping tasks, individually and in groups. Assessing, analysing and comparing the individual and group concept maps constructed, specific influences were identified among them. Based on these data, dependences among individual and group characteritics such as knowledge and style, with individual progress were investigated. Finally, we discuss how factors that reflect individual and group characteristics before, during and after collaboration may inform the learner and group model of the adaptive concept mapping environment COMPASS.


The effects of focal spot size and the nature of powder samples (such as heterogeneous catalysts) on the quality of data obtainable from a dispersive EXAFS experiment are characterized at ID24 of the ESRF. Using examples of supported Pd catalysts, it is shown that, for a given photon flux, massive improvements in data quality can be achieved by increasing the size of the dispersive beam in the vertical, whilst concurrently applying a methodology to account for scattering effects emanating from the samples under study. These improvements are demonstrated using progressively practical and demanding examples. Questions regarding optimal beam dimensions for the study of such materials, how to counter undesirable effects that arise from the coherence of the source, how to obtain similar results consistently across the 5-30 keV bandwidth of ID24, and whether a methodology for simultaneous normalization in dispersive EXAFS is of significant utility in such circumstances are discussed.


In the past, the design of CNC machine tools focused on their functional aspects and was hard to acquire any resonance with customers. Nowadays, despite the needs of low-price and high-quality machine, more and more customers request a good-looking machine. Regarding this, our study aims to provide a novel approach based on the combination of Kansei engineering and support vector machine scheme to determine the best design combination of product form elements of machine tools for matching consumer-preferred product images. Furthermore, for practical consideration, a user-friendly design expert system is developed and an example of new-designed machine tool out-looking based on this system is demonstrated.


Social learning authors pointed out that people behave in a way to imitate the pattern which they evaluate as having high social status or success. The present research was designed to assess the influence of violent films on children and adolescents' aggressive behavior. Experiment I studied 360 adolescents, of both genders, in four groups: one was a control group and the other three watched violent films, with and without a hero, and a nonviolent film. Aggressive behavior was measured in a football game after they had watched the films. Experiment II recorded the aggressive behavior of 160 children, both genders, during a football game, before and after watching a violent and a nonviolent film. The results showed that aggressive behavior of male children and adolescents increased after they had watched the violent film with a hero. This effect was not observed with females. Still, when violence involved sexual, psychological, or physical abuse there was a significant increase in aggressive behavior of both genders. This variable showed positive correlations with antisocial behavior and needs more investigation in the future.


Recently, a bi-dimensional fuzzy entropy measure has been proposed for image texture evaluation. Herein, a new bi-dimensional fuzzy entropy is proposed to process colored images. Our algorithm, FuzEnC2D, in opposition to dos Santos et al. (2018) definition, evaluates each color channel individually with consideration of global and local characteristics. We propose to apply it for the characterization of melanoma's dermoscopic images. In this work, FuzEnC2D is tested by evaluating its sensitivity to change of parameters, rotation sensitivity, ability to determine irregularity through shuffling pixels, and consistency according to different image sizes. For those purposes, white noise and colored Brodatz textures are used. The algorithm is also applied to dermoscopic images of the public PH2 dataset to evaluate its performance in distinguishing common nevi, atypical nevi, and melanoma lesions. The results reveal a relative decrease of, at most, 29.97 % for FuzEnC2D-values when considering different parameters values. On the other hand, the consistency and low rotation sensitivity of the algorithm are revealed by analyzing the same texture with different sizes (maximum relative difference of 4.34%) and when comparing the entropy of an image upon rotation (maximum relative difference of 0.36%). Besides, after shuffling the pixels of an image, FuzEnC2D-values of shuffled images increases up to 8.9 times of the original values. Moreover, using the red channel's entropy, a common nevi lesion is statistically different from an atypical one (p = 0.004 with the Kruskal-Wallis test). Regarding the green channel, a statistical difference (p = 0.034) is observed between atypical nevi lesions and melanoma. Also, differentiating a common nevi lesion from lesions diagnosed as melanoma is possible regardless the RGB channels. Finally, the FuzEnC2D algorithm appears as a promising algorithm to analyze, through an entropy-based measure, the texture of colored images.


Geometric morphometric analysis was used to describe the variations in body shape existing in Sardinellafimbriata sampled from Butuan Bay, Dipolog Bay, and Pagadian Bay in Mindanao, Philippines. A notable degree of significance was detected both within and between populations which is shown by the results obtained from multivariate analysis of variance (MANOVA), canonical variate analysis (CVA), and discriminant function analysis (DFA). Within populations showed sexual dimorphism between the two sexes while geographic isolation may have caused the variations that were detected between the three populations. Additionally, environmental factors such as overfishing/overexploitation and different methods of fishing could also be one of the factors causing these variations. Hence, this study proved the ability of modern geometric morphometrics to distinguish and describe body shape variations existing within and between populations of S. fimbriata. It is recommended, however, that a genetic study regarding these shape variations should be as well conducted to understand more the diversity of this species which would greatly contribute to mananagement strategies of stocks or populations of S. fimbriata.


In SPICE Gummel-Poon models one 1/f-noise source describes the low frequency noise behaviour of bipolar junction transistors (BJTs). In this paper we present a method to extract the respective model parameters from measured 1/f-noise data without the requirement of exactly determining the corner frequency f/sub c/, i.e. the frequency at which the 1/f-noise equals the device noise floor. This novel method is applicable to low-noise as well as to very noisy devices. We present results of different active devices. Verification of the extracted model parameters is done in an oscillator application. Measured and calculated phase noise results agree within measurement accuracy of /spl plusmn/2 dB.


Water policy initiatives often run into difficulties when they encounter the realities of really existing societies. Policies may not get implemented as planned, and may not achieve their stated objectives. Many things happen when policy initiatives travel from formulation to implementation. The papers in this volume examine the travel and appropriation of water policy by looking at the contestation and the embeddedness of water policy. Organised in the sequence everyday politics of water, politics of water policy, hydropolitics, global water politics, the papers constitute a call for a policy approach that replaces a social engineering with a strategic action perspective.


The modern global debt market features historically low average interest rates, convergence of yields on bonds with different maturities, an increase of yield curve inversion emergence frequency and a large-scale trend to automate financial decision making. The researchers' attention in these fields is mainly focused on designing models that describe the state of the debt market as whole or its individual instruments in particular, as well as on risk management methods. At the same time, the specialized literature offers very few works concerning the topic of computer algorithms for bond portfolio selection based on traditional or advanced investment strategies. The aim of the present research is to create a modification of the existing algorithm of riding the yield curve strategy application, employing, first, average bond yield over the holding period instead of traditional bond yield to maturity; second, a developed algorithm for calculating the market spread on bonds; and, third, alternative risk evaluation indicators (compensation coefficients), which allow us to measure objectively price risk, liquidity risk, transaction costs risk and a general risk. The modification and the development of the algorithm for calculating the market spread were carried out using the direct measurement of the result technique, which entails application of the strategy to the data on bond issues received through the Moscow Exchange API. The selection of financial instruments was conducted in all sectors of the Russian debt market: public bonds, sub-federal and municipal bonds, corporate bonds. The modified algorithm enabled us to get extra yield for each selected bond issue, thereby proving the high effectiveness of the technique compared to the traditional strategy. Software implementation of the algorithm can be integrated into any robotized or semi-robotized stock exchange trading application.


As of July 1, the Joint Commission on Accreditation of Healthcare Organizations will require you to assess staffing by using specific indicators based on clinical/service and human resource outcomes. Your ED must have sufficient numbers of qualified staff to care for patients, including direct and indirect caregivers. Nurses must have the required skills to care the for patients they are assigned to. If data reveal inadequate staffing, you must take appropriate action to correct this.


Background. Previous twin studies of hyperactivity have supported a 'contrast effect', whereby the more hyperactive the rating of one twin, the less the rating of the other. It has not been clear whether contrast effects occur in the twins' behaviour or in the ratings made of their behaviour but the implications for hyperactivity are different under the two models. Method. We use hyperactivity ratings from mothers and teachers for 1644 twin pairs in the Virginia Twin Study of Adolescent Behavioral Development (VTSABD) to explore the origin of contrast effects, making use of independent teacher reports in a proportion of twins. Models were fitted separately for the two informants and jointly to ratings combined through a latent variable, using structural equation modelling. Results. Models for maternal data confirm the contrast effect previously reported. Teacher ratings show a different form of bias, with both twin confusion and correlated errors representing alternative but not mutually exclusive explanations of the data. Latent variable modelling of the joint responses allowed comparison of a model in which the contrast effect was placed on maternal ratings, representing bias, versus one in which the contrast occurred in the underlying 'true' phenotype. The fit of the former model was significantly better. Conclusions. Support is provided for the notion of contrast effects as a form of rater bias in maternal hyperactivity ratings. Different bias in teacher reports highlight that no one report can be considered a gold standard. The extent to which such biases may distort information for other data sources such as sib-pair studies of concordance/discordance is discussed.


This paper discusses barriers to the development of academic writing, in the area of teacher education in UK higher education . We first situate these issues in a higher education context increasingly defined by new technologies and diverse cohorts of higher education students. Drawing on empirical data obtained from interviews with both students and teachers (N=21), we then critically examine a range of perspectives on the definition, role and function of academic literacy in this contemporary context.

Findings include useful insights into the development of writing skills and teacher identity, but they also reveal fundamental differences in the epistemological presuppositions of those teaching academic writing. These accounts are reflected in significant differences in pedagogy, and raise important questions for practice which, although potentially irresolvable, may help to explain some of the difficulties which emerge when trying to teach academic writing. Such fundamental issues, we argue, need to be at least recognized if teachers hope to develop the writing capacity of trainee teachers in an academic context.

3rd International Conference on Higher Education Advances, HEAd'17. Universitat Politecnica de Valencia, Valencia.


Given a single trajectory of a dynamical system, we analyze the performance of the nonparametric least squares estimator (LSE). More precisely, we give nonasymptotic expected $l^2$-distance bounds between the LSE and the true regression function, where expectation is evaluated on a fresh, counterfactual, trajectory. We leverage recently developed information-theoretic methods to establish the optimality of the LSE for nonparametric hypotheses classes in terms of supremum norm metric entropy and a subgaussian parameter. Next, we relate this subgaussian parameter to the stability of the underlying process using notions from dynamical systems theory. When combined, these developments lead to rate-optimal error bounds that scale as $T^{-1/(2+q)}$ for suitably stable processes and hypothesis classes with metric entropy growth of order $\delta^{-q}$. Here, $T$ is the length of the observed trajectory, $\delta \in \mathbb{R}_+$ is the packing granularity and $q\in (0,2)$ is a complexity term. Finally, we specialize our results to a number of scenarios of practical interest, such as Lipschitz dynamics, generalized linear models, and dynamics described by functions in certain classes of Reproducing Kernel Hilbert Spaces (RKHS).


Landmark discoveries in molecular oncology have provided a wide-angle overview of the heterogenous and therapeutically challenging nature of cancer. The power of modern 'omics' technologies has enabled researchers to deeply and comprehensively characterize molecular mechanisms underlying cellular functions. Interestingly, high-throughput technologies have opened new horizons for the design and scientific fool-proof evaluation of the pharmacological properties of targeted chemical compounds to tactfully control the activities of the oncogenic protein networks. Groundbreaking discoveries have galvanized the expansion of the repertoire of available pharmacopoeia to therapeutically target a myriad of deregulated oncogenic pathways. Natural product research has undergone substantial broadening, and many of the drugs which constitute the backbone of modern pharmaceuticals have been derived from the natural cornucopia. Baicalein has gradually gained attention because of its unique ability to target different oncogenic signal transduction cascades in various cancers. We have partitioned this review into different sub-sections to provide a broader snapshot of the oncogenic pathways regulated by baicalein. In this review, we summarize baicalein-mediated targeting of WNT/β-catenin, AKT/mTOR, JAK/STAT, MAPK, and NOTCH pathways. We also critically analyze how baicalein regulates non-coding RNAs (microRNAs and long non-coding RNAs) in different cancers. Finally, we conceptually interpret baicalein-mediated inhibition of primary and secondary growths in xenografted mice.


Glucose-regulated stress response of cancer cells occurs during the growth of solid tumors and is induced in culture by treatments with various agents, including 2-deoxyglucose, glucosamine, and calcium ionophore A23187. We previously reported that the three stressors commonly induced cell-cycle arrest in the G1 phase and resistance to antitumor drugs in human cancer A2780 and HT-29 cells. In this study, we investigated the mechanisms of stress-induced G1 arrest by determining the expression of cell-cycle-regulating proteins. Among G1 cyclins and cyclin-dependent kinases (cdk) examined, the expression levels of cyclin D1 preferentially decreased in the stressed cells. A time-course study showed that the decrease in cyclin D1 coincided with the appearance of hypophosphorylated retinoblastoma protein (pRb), which is the growth suppressive form. These findings suggest that the stress-induced G1 arrest is mediated through the down-regulation of cyclin D1-associated kinases (cdk4/6), pRb kinases during G1 phase. This was also supported by decreased cdk4 expression in stressed HT-29 cells. In addition, p21WAF1, a cdk inhibitor, was induced in the stressed cells, particularly A23187-treated cells. A23187, compared with the other stressors, caused extreme pRb hypophosphorylation, suggesting that p21WAf1 is involved in the regulation of pRb phosphorylation in the stressed cells. Our present findings could explain a molecular-based mechanism of a growth-arrested quiescent state and also resistance to chemotherapy of solid tumor cells.


Nanomaterials are commonly defined as engineered structures with at least one dimension of 100 nm or less. Investigations of their potential toxicological impact on biological systems and the environment have yet to catch up with the rapid development of nanotechnology and extensive production of nanoparticles. High-throughput methods are necessary to assess the potential toxicity of nanoparticles. The omics techniques are well suited to evaluate toxicity in both in vitro and in vivo systems. Besides genomic, transcriptomic and proteomic profiling, metabolomics holds great promises for globally evaluating and understanding the molecular mechanism of nanoparticle-organism interaction. This manuscript presents a general overview of metabolomics techniques, summarizes its early application in nanotoxicology and finally discusses opportunities and challenges faced in nanotoxicology.


In federated learning (FL), a machine learning (ML) model is collectively trained by a large number of users, using their private data in their local devices. With top $r$ sparsification in FL, the users only upload the most significant $r$ fraction of updates, and the servers only send the most significant $r'$ fraction of parameters to the users in order to reduce the communication cost. However, the values and the indices of the sparse updates leak information about the users' private data. In this work, we consider an FL setting where $N$ non-colluding databases store the model to be trained, from which the users download and update sparse parameters privately, without revealing the values of the updates or their indices to the databases. We propose four schemes with different properties to perform this task while achieving the minimum communication costs, and show that the information theoretic privacy of both values and positions of the sparse updates can be guaranteed. This is achieved at a considerable storage cost, though. To alleviate this, we generalize the schemes in such a way that the storage cost is reduced at the expense of a certain amount of information leakage, using a model segmentation mechanism. In general, we provide the tradeoff between communication cost, storage cost and information leakage in private FL with top $r$ sparsification.


West Nile virus (WNV) is the most important and widespread mosquito-borne virus in the United States (U.S.). WNV has the ability to spread rapidly and effectively, infecting more than 320 bird and mammalian species. An examination of environmental conditions and the health of keystone species may help predict the susceptibility of various habitats to WNV and reveal key risk factors, annual trends, and vulnerable regions. Since 2002, WNV outbreaks in Wisconsin varied by species, place, and time, significantly affected by unique climatic, environmental, and geographical factors. During a 15 year period, WNV was detected in 71 of 72 counties, resulting in 239 human and 1397 wildlife cases. Controlling for population and sampling efforts in Wisconsin, rates of WNV are highest in the western and northwestern rural regions of the state. WNV incidence rates were highest in counties with low human population densities, predominantly wetland, and at elevations greater than 1000 feet. Resources for surveillance, prevention, and detection of WNV were lowest in rural counties, likely resulting in underestimation of cases. Overall, increasing mean temperature and decreasing precipitation showed positive influence on WNV transmission in Wisconsin. This study incorporates the first statewide assessment of WNV in Wisconsin.