Lysosomes are essential organelles required for breakdown of endocytic and biosynthetic cargo, pathogen killing and autophagy. In most cells, lysosomes are typically small punctate structures. By contrast, innate immune cells like macrophages and dendeitic cells that have been exposed to bacterial lipopolysaccharids (LPS) exhibit strikingly tubular lysosomes (TLs) and lysosome-related major histocompatility class II (MHCII) compartments (MIIC), respectively. TLs are suggested to play a role in phagosome maturation and retention of fluid-phase endocytic uptake in activated macrophages. In addition, the dendritic cell tubular MIIC (tMIIC) may be involved in antigen presentation. Since remarkably little was known about how tubular lysosomes form, I took to investigate the molecular requirements for this process in macrophages and dendritic cells and present my findings in this thesis.
Here I confirm that microtubules are necessary as a template for lysosome tabulation, along with dynein and kinesin microtubule-dependendent motors. We were first to identify molecular components necessary for lysosome tabulation; TL biogenesis required the concerted action of the Ar18b GTPasem along with its effector SKIP, a kinesin adaptor proteins for dynein and kinesin, respectively. Importantly, we observed that TLs are highly dynamic structures whereas punctate lysosomes are conspicuously more static.
I also present evidence that mTOR, a lysosomal protein kinase, is required for LPS-induced TL biogenesis and cell surface delivery of MHCII in macrophages and dendritic cells. First, I show that the MyD88-P13K-Akt-mTOR signaling pathway regulates LPS-induced lysosome tabulation. Second, I demonstrate that mTOR is required for anterograde lysosomal transport suggesting that this kinase may regulate tabulation and antigen presentation by modulating the microtubule-based motor activity of lysosomes.
Finally I present preliminary data on the properties of tubular lysosomes compare to punctate lysosomes in an effort to characterize these organelles. Among the data presented is evidence that total lysosomal volume increases significantly upon tabulation, which may have important underlying implications in antigen sampling and processing.
Overall, my work has expanded on our knowledge on our knowledge of how morphology and trafficking of lysosomes is modulated in immune cells, which may alter cell function.


Bursts of rapid repeated speciation called adaptive radiations have generated much of Earth's biodiversity and fascinated biologists since Darwin, but we still do not know why some lineages radiate and others do not. Understanding what causes assortative mating to evolve rapidly and repeatedly in the same lineage is key to understanding adaptive radiation. Many species that have undergone adaptive radiations exhibit mate preference learning, where individuals acquire mate preferences by observing the phenotypes of other members of their populations. Mate preference learning can be biased if individuals also learn phenotypes to avoid in mates, and shift their preferences away from these avoided phenotypes. We used individual‐based computational simulations to study whether biased and unbiased mate preference learning promotes ecological speciation and adaptive radiation. We found that ecological speciation can be rapid and repeated when mate preferences are biased, but is inhibited when mate preferences are learned without bias. Our results suggest that biased mate preference learning may play an important role in generating animal biodiversity through adaptive radiation.


One of the important and interesting problems in astrophysics and plasma physics is collimation of plasma jets. The collimation mechanism, which causes a plasma flow to propagate a long distance, has not been understood in detail. We have been investigating a model experiment to simulate astrophysical plasma jets with an external magnetic field [Nishio et al., EPJ. Web of Conferences 59, 15005 (2013)]. The experiment was performed by using Gekko XII HIPER laser system at Institute of Laser Engineering, Osaka University. We shot CH plane targets (3 mm × 3 mm × 10 μm) and observed rear-side plasma flows. A collimated plasma flow or plasma jet was generated by separating focal spots of laser beams. In this report, we measured plasma jet structure without an external magnetic field with shadowgraphy, and simultaneously measured the local parameters of the plasma jet, i.e., electron density, electron and ion temperatures, charge state, and drift velocity, with collective Thomson scattering.


At eight weeks of gestation, after ovulation induction and intrauterine insemination, a 32-year-old woman was admitted for pelvic pain and vaginal bleeding. Transvaginal sonographic images were highly suggestive for ectopic ovarian pregnancy: no intrauterine gestational sac with b-hCG serum levels of 4252 IU/mL and inhomogeneous, highly vascularized adnexal-ovarian mass. Ectopic pregnancy was confirmed at laparoscopy which showed an enlarged and highly vascularized right ovary, with no bleeding. The removal of the trophoblastic tissue was complicated by massive bleeding but controlled with the complete removal of the ectopic tissue from the surrounding normal ovary. Histologic examination confirmed the presence of chorionic villi within ovarian tissue. Post-operative recovery was uneventful and the woman was discharged on day-4 (b-hCG serum level 12 IU/mL). Two months later she conceived, with a further spontaneous delivery at term. Early and accurate diagnosis by gray-scale and Power Doppler assessment may permit a conservative laparoscopic sparing surgery of primary ovarian pregnancy.


Evidence is mounting that a significant fraction of the early-type galaxy population contains substantial reservoirs of cold interstellar gas and dust. We investigate the gas and dust in NGC 5485, an early-type galaxy with a prominent minor-axis dust lane. Using new Herschel PACS and SPIRE imaging data, we detect 3.8 × 106 M⊙ of cool interstellar dust in NGC 5485, which is in stark contrast with the non-detection of the galaxy in sensitive H I and CO observations from the ATLAS3D consortium. The resulting gas-to-dust ratio upper limit is Mgas/Md < 14.5, almost an order of magnitude lower than the canonical value for the Milky Way. We scrutinize the reliability of the dust, atomic gas and molecular gas mass estimates, but these do not show systematic uncertainties that can explain the extreme gas-to-dust ratio. Also a warm or hot ionized gas medium does not offer an explanation. A possible scenario could be that NGC 5485 merged with an SMC-type metal-poor galaxy with a substantial CO-dark molecular gas component and that the bulk of atomic gas was lost during the interaction, but it remains to be investigated whether such a scenario is possible.


Perhaps the most iconic feature of melting Arctic sea ice is the distinctive ponds that form on its surface. The geometrical patterns describing how melt water is distributed over the surface largely determine the solar reflectance and transmittance of the sea ice cover, which are key parameters in climate modeling and upper ocean ecology. In order to help develop a predictive theoretical approach to studying melting sea ice, and the resulting patterns of light and dark regions on its surface in particular, we look to the statistical mechanics of phase transitions and introduce a two-dimensional random field Ising model which accounts for only the most basic physics in the system. The ponds are identified as metastable states in the model, where the binary spin variable corresponds to the presence of melt water or ice on the sea ice surface. With the lattice spacing determined by snow topography data as the only measured parameter input into the model, energy minimization drives the system toward realistic pond configurations from an initially random state. The model captures the essential mechanism of pattern formation of Arctic melt ponds, with predictions that agree very closely with observed scaling of pond sizes and transition in pond fractal dimension.


Background: A systematic review on homoeopathic pathogenetic trials (HPTs) from 1945 to 1995 was published in 2007, and the basic question whether the effect produced by homoeopathic drugs in healthy human volunteers is equivalent to placebo or otherwise remained unanswered. There is a need to take up another review of HPTs conducted in the last two decades, to assess the changes in the methodologies adapted and to assess whether the effects produced in apparently healthy volunteers is due to homoeopathic medicines in high dilutions or not. Objective: To seek, collect, review and describe HPTs published during 1996–2018. Materials and Methods: A comprehensive literature search, both electronic and manual, was done using search terms 'homoeopathic drug proving' and 'homoeopathic pathogenetic trial' with time constraint of 1996–2018 in English language. As per the inclusion and exclusion criteria, the papers were selected for extraction of data in the predefined extraction form. Results: One hundred and forty-seven eligible records (74 peer-reviewed [PR] and 73 non-peer-reviewed [NPR]) of HPTs of 214 drugs were identified and subjected to the extraction of data. Majority of the drug proving records were contributed by the Central Council for Research in Homoeopathy which included 86 records (24 PR and 62 NPR) with the data of 24 and 63 drugs, respectively, and by Riley, one book (NPR) with data of 68 drugs. Heterogeneity was encountered in all aspects – design, conduct, participants and outcome reporting.Conclusion: This preliminary study is the basis for data recovery and for the forthcoming program of systematic review and meta-analysis, which may include the HPTs published in other languages.


A dramatic change in cell phenotype is sometimes seen in an advanced stage of mouse skin carcinogenesis when a relatively well-differentiated squamous cell carcinoma progresses to a less differentiated spindle cell carcinoma. This thesis describes a study of some genetic and epigenetic events that may be responsible for the squamous to spindle cell transition using a panel of fixed morphology and plastic morphology cell lines. The experimental approaches used include genetic and cell biology-based studies. An allelotype of clonally related but morphologically distinct cell lines, A5, B9 and D3 was compiled using 118 informative markers and genetic alterations distinguishing the differing cell types have been described. Alterations distinguishing the squamous and spindle cells were found on chromosomes 1, 4, 5, 6, 8, 12, 13, 16, 18 and 19. The most interesting of these with respect to tumorigenesis are on chromosomes 4 and 6; these have been shown to be involved in carcinogenesis in other studies. Although no specific allelic losses were shown to correlate with the squamous/spindle transition, this study has provided information on the lineage of clonally related cell lines from the same tumour and has provided some clues to the gross alterations that may be central to this process. A wide range of biochemical studies have also been used to characterise the fixed morphology cell lines plus additional cell lines which have more plastic morphologies i.e. the SN161 single cell clones. It has been possible to induce the transition from a squamous morphology to a more fibroblast-like phenotype in vitro and in vivo and some of the candidate effectors of this change have been analysed. When the SN161 cell lines are injected into nude mice, they all produce spindle tumours regardless of their morphology in vitro. Explants from tumours induced by squamous cell lines can regain their squamous morphology when grown in normal culture conditions. It seems that some factor present in vivo is encouraging the spindle phenotype; alternatively some factor present in vitro could be encouraging the squamous phenotype. Specific extracellular factors were shown to influence the morphology of SN161 derived cell lines. Growth on fibronectin coated plates made the spindle cells more fibroblast-like but had no effect on the squamous cells. The same was true for Matrigel coated plates. The most interesting result was found with TGF? treatment of the cells. This induced the squamous cell lines, EIN and E4, to become fibroblast-like and caused their E-cadherin to become delocalised and its expression reduced. This observation was consistent with the appearance of the spindle morphology. This system can now be used to study the immediate consequences of changes of morphology rather than secondary changes which can complicate results based on the study of spindle tumours.


Objective: The aim of this study was to investigate the toxicity; analgesic and anti-pyretic properties of standardized HA methanolic extract (HAMeOH) in vivo. Methods: The acute toxicity study was performed on rats while adopting the OECD-420 Guidelines (fixed dose procedure). Assessment of analgesic activity was performed in rats with two analgesic models. One was acetic acid induced writhing response and the other formalin-induced paw licking. The anti-pyretic effect was tested by Brewer's yeast induced fever in rats. Results: For the acute toxicity test, the higher dose administration of 2000 mg/kg bw. of H.albus did not produce any toxic signs or deaths in rats. There were no significant differences (p>0.05) in the body and organ weights between control and treated groups. The (LD50) of "H.albus" was higher than 2000 g/kg bw. In subacute toxicity study, no mortality and toxic signs were observed with the doses of 100 and 200 mg/kg bw. of extracts of for 28 consecutive days. These analgesic experimental results indicated that HAMeOH (100 mg/kg and 200 mg/kg) decreased the acetic acid-induced writhing responses and HAMeOH (100 mg/kg and 200 mg/kg) decreased the licking time in the second phase of the formalin test. Moreover, in the model of yeast induced elevation of the body temperature HAMeOH showed dose-dependent lowering of the body temperature up to 3h at both the doses these results obtained, were comparable to that of paracetamol. Conclusion: The present findings indicate that the leaves of Hyoscyamus albus L. possess potent analgesic and antipyretic activity.


ABSTRACT Under conditions of constant sediment supply (S) to the basin and a steady rate of rise (A) in relative sea level, the autoretreat theory predicts that shorelines can retreat landwards at a relatively early stage of delta growth and attain an "autobreak" state, after which the existing subaqueous slope begins to be starved of sediment and thereby lose its clear delta-front configuration. A numerical model based on this theory further suggests that shoreline migration depends on the inclination of basin's basement slope () and subaqueous depositional slope () and, to a lesser degree, on the inclination of subaerial depositional slope (). Two-dimensional flume experiments in which a miniature delta is subject to steady forcing (A = const > 0, S = const > 0), were conducted to test the expectations of the autoretreat theory. The experiments consisted of two different series of runs: one was of " modulation" associated with a narrow range of the ratio of water discharge to sediment discharge (q/S), the other was of "q/S modulation" with kept nearly constant. The q/S ratio was mostly responsible for changes in but also affected to some extent. All experimental runs substantiated the landward turnaround feature of shoreline accretion (i.e., autoretreat) and the geometrical break of the delta-front shape during its retreat phase (i.e., autobreak). The obtained shoreline trajectories hold their geometrical patterns even after they were nondimensionalized in terms of the S/A ratio. A key hypothesis confirmed in the experiments is that A and S can never balance each other. Both of the experimental series brought some systematic change of shoreline trajectories, but the variations of shoreline trajectory due to modulation were much more striking than those related to q/S. Even these contrasting results are consistent with the numerical predictions. The present experimental results support the applicability of the autoretreat concept to natural environments and help clarify the processes governing the regression and transgression of a shoreline on a constructional margin.


COPD is often accompanied by other chronic diseases that are also associated with systemic inflammation, such as obesity, diabetes, and arteriosclerosis. Recent data indicate that nocturnal oxygen desaturation and coexisting metabolic syndrome are related to systemic inflammation in patients with COPD. Alveolar hypoxia and consequent hypoxemia increase in prevalence as COPD severity increases. Chronic hypoxemia contributes to the development of adverse sequelae of COPD, such as pulmonary hypertension, atherosclerosis, lung microbiome diversity and systemic inflammation. COPD is a heterogeneous disease with airway inflammation driven by bacterial infections, few studies to date they examined microbiology or infection. The introduction of cultureindependent techniques for the microbiological analysis of respiratory samples confirmed that respiratory system hosts a large number of microorganisms, which include a wide range of bacteria. Regular exposure to tobacco smoke, lifestyle and food pattern can change the microbiome in healthy smokers and at-risk COPD patients, increasing the presence of a limited number of genres that reach a high relative abundance, a pattern, which can be considered as a dysbiosis. We assume that in patients with COPD and concurrent obesity and lung dysbiosis at least three factors play a role in the systemic inflammatory syndrome. Recent data showed that changes in the lung microbiome are associated with numerous exacerbations of COPD and are involved in mediating inflammatory responses of the host in some patients. Further research should elucidate the complex relationship between obstructive lung disease, obesity and lung microbiome diversity systemic inflammation accompanying these different conditions, and the causative role of systemic inflammation in obese COPD with nocturnal oxygen desaturation.


ABSTRACT Precise time constraints of the main extrusive phase of the Emeishan large igneous province (ELIP) remain unresolved because basalts commonly do not contain suitable minerals for U–Pb dating, whereas previous 40Ar/39Ar studies on basalts yielded tectonothermal overprint ages. The timing for the ELIP was deduced from indirect dating of minor intrusions of ultramafic/mafic and felsic compositions by geochronological methods and geological correlations. The extrusive part of the ELIP consists of an older low-Ti and younger high-Ti basalt phases. We have found fresh samples of plagioclase-phyric rocks at the lower Qiaojia extrusive section (the Yunnan province of China), which belong to the ELIP unit of the high-Ti basalt series. 40Ar/39Ar dating on plagioclase from two samples conducted at two different laboratories using different age standards yielded statistically indistinguishable results with the weighted mean age of 260.1 ± 1.2 Ma for five individual measurements. This provides the direct constraints on the onset of the ELIP high-Ti basalt extrusive phase. The obtained age is within the error or slightly older than the age of the Guadalupian–Lopingian boundary and felsic ignimbrite capping the ELIP lava succession (both dated at 259.1 ± 0.5 Ma). Our new data are strengthening the short duration of the, at least, high-Ti phase of the ELIP volcanism and its temporal link with the end-Guadalupian mass extinction. Estimation of the total duration of the ELIP volcanism awaits finding of suitable for dating low-Ti basalts.


OBJECTIVE
Genes, involved in the modulation of inflammatory response and bone remodeling, play a role in the development of postorthodontic external apical root resorption (EARR). The aim of our study was to analyze possible associations between seven single nucleotide polymorphisms (SNPs) in interleukin-17A (IL-17), osteopontin (SPP1), purinoreceptor P2X7 (P2RX7), and tumor necrosis factor receptor superfamily member 11B (TNFRSF11B) genes and EARR in children after orthodontic treatment.

SUBJECTS AND METHODS
This case-control study comprised 99 orthodontically treated patients (69 controls and 30 subjects with EARR). Genotype determinations of rs2275913, rs11730582, rs9138, rs208294, rs1718119, rs3102735, and rs2073618 were based on polymerase chain reaction using 5' nuclease TaqMan® assays.

RESULTS
While no significant differences were observed in allele or genotype frequencies of all seven studied SNPs, specific haplotype of P2RX7 (rs208294 and rs1718119) modified the risk of EARR development (P < 0.05). In addition, the length of treatment with a fixed orthodontic appliance positively correlated with the presence of EARR (P < 0.05).

CONCLUSIONS
Although the effect of individual SNPs studied on the EARR development was not confirmed in the Czech population, complex analysis suggested that variability in the P2RX7 gene and the length of orthodontic treatment may be important factors contributing to the etiopathogenesis of postorthodontic EARR.


Dark, windblown (eolian) sand on Mars has produced significant geologic effects throughout Martian history. Although local and regional sand sources have been identified, a primary origin, or genesis, for Martian sand has not been demonstrated. This knowledge gap was recently heightened by the discovery of widespread sand motion, implying breakdown of grains to sub-sand sizes. To address the question of sand genesis, we investigated the source(s) of sand in Aeolis Dorsa (AD), the westernmost Medusae Fossae Formation, using comparisons to sand potentially sourced from multiple regions, each connoting a different sand genesis. Our methods included comparison of (1) AD sand mineralogies with those of possible sand source features, and (2) mapped AD sand deposits and inferred emplacement directions with modeled sand deposit locations and transport pathways. The results point to a time-transgressive unit, interpreted as pyroclastic, as a source of dark sand. High-resolution images of this unit reveal outcrops with dark sand weathering out of lithified bedrock. Given the extent of interpreted pyroclastic deposits on Mars, this sand genesis mechanism is likely widespread today and operated throughout Martian history. Whereas this work identified olivine-rich sand, a range of original pyroclastic lithologies would account for the mineralogic variability of dune fields on Mars. These findings can be tested through analyses of other pyroclastic deposits and potentially by data from the NASA Curiosity rover in nearby Gale crater.


SUMMARY Breeding trials for swede (Brassica napus var. napobrassica) in 2000–2010 showed that 0·85 of the incidence of brown heart (BH) in the trials was associated with genotypes that are progeny of Ag31, Or13 and Me77c. In order to investigate this and the effect of treatment with boron (B), established varieties and improved parent lines carrying male sterility (ms), and their F1 hybrids (test hybrids), were grown in a field trial in the UK in 2011 and subjected to four B treatments (0·00, 1·35, 1·80 and 2·70 kg B/ha). The results confirmed that BH incidence and severity was affected by genotype but could be ameliorated by B application. Genotype Ag31 was very susceptible while Or13 and Me77c were of intermediate susceptibility and the hybrids between susceptible parents were also sensitive. Genotypes Gr19 and Ly01 were highly resistant even in the absence of B application. Hybrids between resistant and susceptible lines were highly resistant. The use of ms had no influence on BH. Resistance to BH was a dominant trait: homozygous dominant (BHBH) or heterozygous (BHbh) genotypes confer this trait, while susceptibility is recessive (bhbh). Some quantitative variation existed, suggesting that resistance was not a single gene effect. There was a significant negative correlation (r=−0·632) between root B content and the severity of BH in susceptible genotypes. Severe BH was associated with 12–21·5 μg B/g of root dry weight at zero B applied. Moderate discolouration was associated with 19·5–24·8 μg B/g recorded at moderate B applied and only Ag31 showed BH at 2·70 kg B/ha. Resistant varieties had root contents of 23 μg B/g or more while susceptible varieties required a minimum of 31 μg B/g to offset BH.


This paper focuses on the Agreement for the Establishment of the African Continental Free Trade Area (AfCFTA). It argues that commercial activities in precolonial Africa was akin to the phenomenon of lex mercatoria in medieval Europe. It discusses two major tenets embedded in the AfCFTA: the variable geometry principle and the dispute settlement mechanism. It argues that for structural and comparative purposes, these principles (variable geometry and dispute settlement) form the kernel of modern lex mercatoria in the African context. This paper concludes by advocating that the AfCFTA will enhance the principles of lex mercatoria by promoting African trade principles.


Control Networks for Nepal was originally defined through the use of conventional measurements. Conventional mapping methods have led to a static and inactive networks of control point. This network of control served us very well until the devastating earthquake hit Nepal and disturbed it. Determination of precise ground locations is essential for various tasks such as engineering works, earth observation, location-based technologies, emergency service providers, etc. Global Navigation Satellite System plays a very important role in providing quick and reliable positioning/navigation data. The term 'global navigation satellite system' (GNSS) refers to a constellation of satellites providing signals from space transmitting positioning and timing data. These systems use the principle of trilateration to calculate the location of a user, through the information obtained from a number of satellites. Each satellite transmits coded signals at precise intervals. In principle, three satellites must be available to determine a three-dimensional (x,y,z) position , additional fourth signal is necessary for precise location of a single point. This helps in eliminating the time differences between satellite's atomic clocks and the receiver's clocks. USA in around 1970's started the use of Global Positioning System(GPS). Geodetic Survey Division under Survey Department commenced the use of GPS technology in 1991 A.D as a method for survey technology. Survey Department initiated the use of GPS for carrying out survey of the previously established high order control points. Transformation Parameters (TP) between the National Co-ordinate System and WGS-84 System was derived using the initial Control points co-ordinate and co-ordinate of the same Control points obtained from GNSS survey. GNSS has been used for establishing, updating and rehabilitation of Control Network, measure shift in location produced by earthquake and for various survey task carried out by Survey Department.


The aim of this study is to describe the histologic architecture of the tissues corresponding to the surgically developed connective tissue bundle commonly referred to as the posterior leaf of the vesico-uterine ligament (VUL), and to examine distribution of ganglion cells. Serial macroscopic slices, each 15–20 mm in thickness, were made from eight specimens (obtained from six female elderly cadavers). In these macroslices, the location of the deep uterine vein was used to identify the deep leaf of the VUL. The specimens were trimmed and semi-serial histologic sections in thickness were prepared at 1 mm intervals. Vesical veins and the associated nerve elements were enclosed by fascia and formed a common pedicle. The base of the pedicle contained the deep uterine vein trunk. The fascia encircling the pedicle varied in thickness and connective intensity between specimens. This vesical neurovascular bundle contained abundant ganglion cells. On average, 48.0% of the ganglion cells along the vesical tributaries of the deep uterine vein were located on the medial or vaginal side of the veins, 19.2% were located between veins, 13.0% on the lateral side of the veins, and 19.8% on the dorsal side. The interindividual variability was greatest on the dorsal side of vesical veins and ranged 11–202 cells. We conclude that in order to achieve maximal preservation of the ganglion cells during the surgical dissection of the posterior leaf of the VUL, care must be taken when the medial or vesical aspect of the ligament is separated. The standard nerve-sparing radical hysterectomy should be modified to reflect differences in the distribution of ganglion cells and in connective intensity between ganglions and veins.


The use of multiple antennas at base stations and user devices is a key component in the design of cellular communication systems that can meet the capacity demands of tomorrow. The downlink transmission from base stations to users is particularly limiting, both from a theoretical and a practical perspective, since user devices should be simple and power-efficient, and because many applications primarily create downlink traffic (e.g., video streaming). The potential gain of employing multiple antennas for downlink transmission is well recognized: the total data throughput increases linearly with the number of transmit antennas if the spatial dimension is exploited for simultaneous transmission to multiple users. In the design of practical cellular systems, the actual benefit of multiuser multiantenna transmission is limited by a variety of factors, including acquisition and accuracy of channel information, transmit power, channel conditions, cell density, user mobility, computational complexity, and the level of cooperation between base stations in the transmission design. The thesis considers three main components of downlink communications: 1) estimation of current channel conditions using training signaling; 2) efficient feedback of channel estimates; and 3) allocation of transmit resources (e.g., power, time and spatial dimensions) to users. In each area, the thesis seeks to provide a greater understanding of the interplay between different system properties. This is achieved by generalizing the underlying assumptions in prior work and providing both extensions of previous outcomes and entirely new mathematical results, along with supporting numerical examples. Some of the main thesis contributions can be summarized as follows. A framework is proposed for estimation of different channel quantities using a common optimized training sequence. Furthermore, it is proved that each user should only be allocated one data stream and utilize its antennas for receive combining and interference rejection, instead of using the antennas for reception of multiple data streams. This fundamental result is proved under both exact channel acquisition and under imperfections from channel estimation and limited feedback. This also has positive implications on the hardware and system design. Next, a general mathematical model is proposed for joint analysis of cellular systems with different levels of base station cooperation. The optimal multicell resource allocation can in general only be found with exponential computational complexity, but a systematic algorithm is proposed to find the optimal solution for the purpose of offline benchmarking. A parametrization of the optimal solution is also derived, creating a foundation for heuristic low-complexity algorithms that can provide close-to-optimal performance. This is exemplified by proposing centralized and distributed multicell transmission strategies and by evaluating these using multicell channel measurements.


Spatial equity studies measuring urban service access have been conducted in variety of modern settings, but this research has not been extended to premodern cities. This article presents an exploratory, transdisciplinary pilot study of service access in six premodern urban environments to better understand the historical origins of inequality. Using archaeological and historical spatial data, neighborhood and household access to three types of service facility is studied across different urban traditions. Findings reveal that the size, shape, and spatial structure of cities may influence service accessibility as much as political influence over facility siting or residential choice. Most cities display a spatially concentric pattern of accessibility, and denser cities tend to display more equitable service access. Elite groups possess consistently better service access than nonelite groups. Although this exploratory study must be expanded to produce firmer results, it indicates the importance of interpreting modern urban inequalities from a long-term perspective, and points to the efficacy of comparative, spatially oriented, urban historical research for generating new insights into urban processes.


This paper uses the interval data model to explore the determinants of uncertainty in two-way payment ladder and in multiple-bounded uncertainty choice surveys. It estimates the uncertainty function that relates the size of the willingness-to-pay range to explanatory variables, where one of them is a proxy of the actual willingness-to-pay. The combination of the interval data model and the inclusion of the proxy variable present some advantages over the ordinary least square estimations currently used in the literature. In particular, it reduces the risk of the omitted variable bias and it takes into account that the dependent variable is not fully observed.


In this paper, we propose a COVID-19 epidemic model with quarantine class. The model contains 6 sub-populations, namely the susceptible (S), exposed (E), infected (I), quarantined (Q), recovered (R), and death (D) sub-populations. For the proposed model, we show the existence, uniqueness, non-negativity, and boundedness of solution. We obtain two equilibrium points, namely the disease-free equilibrium (DFE) point and the endemic equilibrium (EE) point. Applying the next generation matrix, we get the basic reproduction number (R0). It is found that R0 is inversely proportional to the quarantine rate as well as to the recovery rate of infected subpopulation. The DFE point always exists and if R0 < 1 then the DFE point is asymptotically stable, both locally and globally. On the other hand, if R0 > 1 then there exists an EE point, which is globally asymptotically stable. Here, there occurs a forward bifurcation driven by R0 . The dynamical properties of the proposed model have been verified our numerical simulations. © 2023 the author(s).


This paper discusses a formal study conducted in 2001 at Brigham Young University to determine the value of the library to the university community. Methods used to collect data for the study included an e-mail survey, usage statistics, naturalistic observations, and interviews. Two years after the study, the authors wondered if the conclusions of the study were still valid. Replicating the original study was impossible, but certain data were readily available for comparison. The comparable data are presented and analyzed. Two new services implemented in response to student requests and their possible influence on continued library usage are presented.


Scientific understanding regarding causes of climate change is maturing. Earlier indications that atmospheric CO2 is the primary cause have been challenged by recent studies. Evidence against anthropogenic global warming is mounting. Subsidized alternative fuel initiatives may run out of support once political opinion aligns with scientific realities. First steps toward policy statements within professional organizations that reflect our current understanding of forces driving climate change are called for. We as farm or timberland managers, investors, lenders, appraisers or consultants in these fields should update our understanding. Agriculture's potential contribution toward cost effective alternative fuel sources and energy independence is discussed.


Objective. To clarify and quantify the effect of thiazolidinediones (TZDs; e.g., pioglitazone, rosiglitazone) on the risk of bladder cancer, other selected cancers, and overall cancer in patients with type 2 diabetes, we performed a systematic review and meta-analysis of observational studies. Methods. A PubMed/MEDLINE search was conducted for studies published in English up to June 30, 2012. Random-effect models were fitted to estimate summary relative risks (RR). Results. Seventeen studies satisfying inclusion criteria (3 casecontrol studies and 14 cohort studies) were considered. Use of TZDs was not associated to the risk of cancer overall (summary RR: 0.96; 95% confidence interval [CI]: 0.91–1.01). A modest excess risk of bladder cancer was reported in pioglitazone (RR: 1.20; 95% CI: 1.07–1.34 from six studies) but not in rosiglitazone (RR: 1.08; 95% CI: 0.95–1.23 from three studies) users. The RRs of bladder cancer were higher for longer duration (RR: 1.42 for2 years) and higher cumulative dose of pioglitazone (RR: 1.64 for 28,000 mg). Inverse relations were observed with colorectal cancer (RR: 0.93; 95% CI: 0.90 – 0.97 from six cohort studies) and liver cancer (RR: 0.65; 95% CI: 0.48 – 0.89 from four studies), whereas there was no association with pancreatic, lung, breast, and prostate cancers. Conclusions. Adequate evidence excludes an overall excess cancer risk in TZD users within a few years after starting treatment. However, there is a modest excess risk of bladder cancer, particularly with reference to pioglitazone. Assuming that this association is real, the potential implications on the riskbenefit analysis of TZD use should be evaluated. TheOncologist 2013;18:148 –156


Olfactory dysfunction increases with disease severity in Alzheimer's disease (AD), is early and independent of disease severity in Parkinson's disease (PD), but is absent in progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). Previous histopathologic studies of olfactory bulbs in AD have shown neurofibrillary tangles (NFTs) and senile plaques while Lewy bodies (LBs) have been described in PD. Little is known about olfactory bulb pathology in PSP and CBD. Tau and alpha-synuclein pathology was assessed with immunohistochemistry in olfactory bulbs of AD (N=15), Lewy body disease (LBD; N=10), LBD with concurrent AD (AD/LBD; N=19), PSP (N=27), CBD (N=3) and cases with no significant neurodegenerative pathology (NSP; N=15). The Braak NFT stage, counts of senile plaques and NFT in cortical and hippocampal sections, and counts of LBs in amygdala and cortical sections were recorded for each case. Apolipoprotein E (APOE) genotypes were determined on DNA prepared from frozen brain tissue. All AD and AD/LBD cases and nine of 10 LBD cases had tau pathology in the anterior olfactory nucleus (AON), but it was uncommon in PSP (9/27), CBD (0/3) and NSP (5/15). Multiple linear regression analysis demonstrated that tau pathology in the AON correlated with Braak stage (P<0.001), cortical LB counts (P<0.001), as well as APOE epsilon4. Tau pathology is common in the olfactory bulb of AD and LBD but is minimal or absent in PSP and CBD. It correlates with APOE epsilon4, severity of tau pathology in the brain and surprisingly with cortical and amygdala LBs, suggesting a possible synergistic effect between tau and synuclein in the AON in cases with both pathologic processes.


Background: The aim was to evaluate safety aspects of patient-controlled sedation and analgesia (PCS) for extracorporeal shockwave lithotripsy (ESWL) and PCS to be handled by non-anaesthesiology doctors. Methods: Thirty-four ASA I-III patients used PCS with propofol and alfentanil for ESWL in this interventional study. Strict safety limits were defined regarding respiratory rate (RR), heart rate (HR), mean arterial blood pressure (MAP), oxygen saturation from pulse oximetry (SpO2), and transcutaneous partial pressures of oxygen (PtcO2) and carbon dioxide (PtcCO2). The patients' levels of consciousness was graded on a five-point scale and monitored with Bispectral Index (BIS). A nurse anaesthetist was supervising the procedure but was instructed to intervene only if safety limits were breached. No supplementary oxygen was given. Results: All patients responded to verbal stimuli during treatment. Cardiovascular stability was maintained, but respiratory variables were affected. Two patients with SpO2 2 ≥ 6.5 kPa). In 18 patients hypoxaemia was indicated as PtcO2 ≤ 8.0 kPa. All these 18 patients were given supplementary oxygen. There was no correlation between dose of drugs, age, weight or any vital variable. The 34 patients would use PCS again in the case of future treatment. Conclusions: During ESWL treatment PCS can be used with good patients' satisfaction, and maintained cardiovascular stability, but PCS had an indisputable effect on pulmonary function with hypoxemia (resulting in need for supplementary oxygen) or hypercarbia. The person in charge of PCS must therefore be trained to perform according to the guidelines for sedation and/or analgesia by non-anaesthesiology doctors.


Speaking has been the main point of interest for many researchers because it is the foremost important skill by which learners are judged. Since speaking is learned through instruction, it has always needed an appropriate method of teaching. The present study made an attempt to investigate the effect of utilizing problem-solving tasks as an approach to teaching and learning the second language on the improvement of speaking skill. In this experimental research, two intact groups of 21intermediate EFL learners in English language institute were involved. The participants were given a TOEFL (PBT) general proficiency test to ensure their level as intermediate at the outset. Two groups were randomly assigned to the control and experimental groups and then, an FCE pre-test of speaking skill was administered to both groups to ensure their homogeneity prior to treatment. Consequently, two groups were instructed for 18 sessions (two months) with different approaches. The control group was taught using the audio-lingual method of teaching and the experimental group was taught using problem-solving tasks. Finally, a post-test of speaking was administered to both groups to assess their speaking ability at the end of research. To compare the participants' speaking ability in the experimental and control groups an independent-samples t-test was conducted. The data analysis showed that the experimental group outperformed on improving their speaking skills post-test compared to the control group. The results showed that utilization of problem-solving tasks has a significant effect on improvement of learners' speaking proficiency.


The concentrations and isotopic compositions of helium, neon, and argon were measured in 29 water samples collected from five superposed aquifers in the Paris Basin (Ypresian, Albian, Neocomian, Dogger, and Trias). In all these groundwater flow systems the data showed excesses of 3He, 4He, and 40Ar above the solubility equilibrium with the atmosphere (air saturated water (ASW)), as well as vertical concentration gradients of these isotopes throughout the basin. The water of the Dogger and the Trias formations also had a 21Ne excess above ASW values. The mean rate of radiogenic and nucleogenic isotope production in the entire sedimentary sequence of the basin cannot produce the measured quantities of 3He, 4He, 21Ne, and 40Ar, if reasonable water residence times are considered. The total calculated production is estimated to represent less than about 13% of the measured values for all isotopes. The greater part (>87%) of the radiogenic and nucleogenic noble gas isotopes is thus believed to originate from the bedrock, and the isotopes are transported vertically through the entire basin. Three mechanisms of transport are considered: advection, dispersion, and molecular diffusion. For the Trias the radiogenic/nucleogenic production ratios of 4He/40Ar and 21Ne/40Ar are close to the mean production rate in the crust (4 ± 3 and 0.96 × 10−7, respectively). For the overlying Dogger, however, these ratios are much higher (4He/40Ar: 10 to 70; 21Ne/40Ar: 8 × 10−7 to 23 × 10−7). We suggest that differences in the vertical diffusive flux of 4He, 21Ne, and 40Ar are the reason for the high isotope ratios observed in the Dogger. In the vertical direction, 4He is transported mostly by diffusion, whereas 40Ar is transported mostly by advection. Neon 21 represents an intermediate situation. The distribution of 3He, 4He,21Ne, and 40Ar throughout the basin can be explained by the existence of only two sources: an atmospheric component contributed by recharge water and a radiogenic/nucleogenic component originating mainly in the bedrock. This concept is supported by two‐dimensional cross‐section modeling of the water flow in the Paris Basin and the advective, dispersive, and diffusive transport of these noble gases in its multiaquifer system presented in part 2 of this study.


There is evidence that L1 and L2 lexical engagement of novel items occurs in adulthood. However, previous studies have not addressed the effects of individual differences on that engagement. Hence, it is unknown how individual differences may influence semantic lexical engagement gains in L1 and L2 adult learners. This study investigates the effects of pre-existing vocabulary knowledge on L2 semantic lexical engagement of recently learned novel words. A semantic priming experiment, across two consecutive days, was conducted. A group of advanced L2 learners (n=26) and L1 learners (n=26) participated in the study. They were trained on pseudowords acting as verbs (n=7) and nouns (n=7). Vocabulary knowledge was measured via an online vocabulary size test. On day one, participants learned the meaning of the pseudowords via reading 12 repetitions of the novel words embedded into English sentences. Immediately, after the reading session, participants undertook surprise recognition and recall vocabulary posttests. On day two, participants took part in a semantic lexical decision task (LDT) with priming to test L2 semantic lexical engagement of the novel words learned on day one. The data were analysed through a series of general and linear mixed-effects models. The results showed that L1 and L2 participants engaged the meaning of the recently learned novel words. Previous vocabulary knowledge predicted faster recognition of semantic related and unrelated primes in the LDT task. It is concluded that L1 and L2 adult learners lexically engaged the meaning of the recently learned words and that vocabulary size is a predictor of L2 semantic lexical engagement of novel words within the conditions of this study. The empirical findings provide a new understanding of the role vocabulary knowledge on L1 and L2 semantic lexical engagement of


Based on the theory of irreversible process thermodynamics, non-linear stress-strain-temperature equations are derived, together with an expression for time-temperature equivalence. In addition, an equation of shift factor for time-temperature equivalence is also obtained. The parameters in the equations are experimentally determined and the main curves for creep compliance and cohesion of TGP granite are obtained by a series of creep tests. It is proved that both deformation and strength of the TGP granite follow the time-temperature equivalent principle.


Although some critics have identified two phases in the poetry of James Wright and have isolated particulars of his movement from traditional to more experimental forms, few have noted also the elements of constancy in the evolution of his poetry. In this first comprehensive scholarly introduction to Wright's work, Stein traces the unified growth of Wright's poetry, asserting that while stylistic changes are often more apparent than actual, Wright does undergo a continuing personal and aesthetic development throughout his career. Stein examines the entire body of Wright's poetry, including such previously unpublished materials as the collection Amenities of Stone. Stein locates Wright in the Emersonian tradition which sees struggle with language as a struggle with the self -- a locating and defining of the self within a world of natural facts. Language, then, becomes a means of self-definition, and to be frivolous or irresponsible with language becomes a negation of the self and the world it inhabits. For Wright, \u201cthe poetry of a grown man\u201d issues from this understanding. Because Wright joins the act of language with the act of selfhood, it is not surprising that the mode and tenor of his work would alter as the self redefines its values and goals, its very identity. In fact, Stein divides Wright's career into three interrelated stages of development: \u201ccontainment,\u201d in which he relies on traditional religious and rhetorical measures to distance himself from a world of experience; \u201cvulnerability,\u201d in which he enters the experiential world where the self is rewarded and equally threatened; and \u201cintegration,\u201d in which he accepts and balances the necessary combination of beauty and horror inherent in being human within a natural world. Stein shows that throughout his career Wright's presiding concern is to discover a way of writing and a way of life that might overcome the effects of an individual's separation from the human community, the natural world, and the spiritual presence in the universe. In Wright's world, to do less is to betray one's language -- and one's self.


The present study has been carried out from the NGHP sediment core (NGHP-01-17A) of northeast Indian Ocean on different siliceous microfossils represented by diatoms and radiolarians along with calcareous nannofossils. Samples from the bottommost subunit Ic of the sediment core (684.09 mbsf to 369.62 mbsf) have been analysed. This contribution is the first comprehensive account on the Tortonian diatom assemblages from the offshore of northeast Indian Ocean that has been integrated with the radiolarian zonations. For determining the relative age of the sequence more precisely the obtained dataset also have been correlated to the calcareous nannofossil zones and eventually an attempt has been made to establish an integrated biostratigraphy. Detailed taxonomic analysis of the diatoms reveals the presence of 118 diatom taxa belonging to 49 genera. Three diatom biozones have been determined using CONISS cluster analysis. Based on the index radiolarian taxa in the studied samples, the entire sequence is assignable to RN6, RN7 and RN8 zones. The samples also contain stratigraphic marker taxa of calcareous nannofossils that allow identifying NN9, NN10 and NN11 zones corresponding to CNM13 - CNM16 zones. The ages of the bottommost and topmost sample of the analysed section of the core have been estimated < 10.49 Ma and > 7.39 Ma respectively. To estimate the sedimentation rate an age-depth model has been proposed using diatom, radiolarian and calcareous nannofossil events. All the microfossil assemblages of the present study have been correlated with the known assemblages of late Miocene, specifically Tortonian from DSDP, ODP, IODP expeditions and onshore sediments of Indian Ocean as well as equatorial Pacific Ocean. Diversity analysis has been carried out to quantitatively estimate the diversity and dominance of the diatom taxa. Planktic/benthic ratio of the diatoms has been calculated to evaluate the water depth.


As a common lethal disease, cancer is now responsible for the majority of deaths worldwide and has been the single most important barrier to increasing life expectancy in the world. The pathogenesis of cancer has been the key point of cancer therapeutics research. The primary cilium, a solitary microtubule-based organelle, is considered to be an important sensor for receiving mechanical and chemical stimulation from other cells and environments; it plays an important role in a variety of signal transduction and disease processes. More importantly, the primary cilium can also function as an elaborate structure to regulate cell proliferation because ciliogenesis regulates cell division by sequestering the centriole. Recently, many new findings have suggested that the length and incidence of the primary cilium are closely connected to carcinogenesis and responses to cancer therapy. Here, we review relevant evidence proving that the primary cilium plays a key role in the occurrence and treatment of cancer. We also summarize the primary cilium-associated signaling pathways in cancer, including Wnt signaling, Hedgehog signaling, PDGFR signaling, and Notch signaling, and anticipate that targeting proteins localized in the primary cilium may be a potential anti-cancer strategy.


Complex systems are often decomposed into modular subsystems for engineering tractability. Although various equation based white-box modeling techniques make use of such structure, learning based methods have yet to incorporate these ideas broadly. We present a modular simulation framework for modeling homogeneous multibody dynamical systems, which combines ideas from graph neural networks and neural differential equations. We learn to model the individual dynamical subsystem as a neural ODE module. Full simulation of the composite system is orchestrated via spatio-temporal message passing between these modules. An arbitrary number of modules can be combined to simulate systems of a wide variety of coupling topologies. We evaluate our framework on a variety of systems and show that message passing allows coordination between multiple modules over time for accurate predictions and in certain cases, enables zero-shot generalization to new system configurations. Furthermore, we show that our models can be transferred to new system configurations with lower data requirement and training effort, compared to those trained from scratch.


Abstract In this paper, I examine the traditional distinction among distributive predicates, mixed predi- cates, and collective predicates, focusing on mixed predicates and collective predicates. Under the traditional three-way distinction of predicates, a mixed predicate can be both a collective predicate and a distributive predicate because a plural noun in a mixed-predicate sentence is ambiguous be- tween a distributive reading and a collective reading. In this paper, adopting Winter's (2002) analysis of set/atom predicates, I argue that mixed predicates are atomic predicates, whereas col- lective predicates are set predicates in Japanese. Support for my proposal comes from distributive and collective readings in the Japanese Floating Quantifier Construction (henceforth, JFQC). When a verb composes with a classifier to denote a set of sets in the JFQC, there is a sharp contrast between the mixed-predicate JFQC and the collective-predicate JFQC, which is problem- atic for Link 1983 and Landman 1989. When a verb composes with a classifier to denote a set of sets in the JFQC, a mixed predicate, which is an atom predicate, can have only a distributive read- ing, whereas a collective predicate, which is a set predicate, can have both a distributive reading and a collective reading. In my analysis, this difference can be reduced to the properties of an atom predicate and a set predicate, as proposed by Winter (2002).


Perinatal infection due to viral agents from mother to neonate is still a major cause of viral transmission in developing countries. Several type of viruses which are known to be transmitted vertieally or perinatally from mother to neonates are: Hepatitis B virus, Herpes simplex, Rubella and Cytomegalovirus. In attempt to estimate the real problem of viral diseases which are vertically or perinatally transmissible among infants, a survey on sero-virology of several type viral antigens among neonates who were borned in Dr. Cipto Mangunkusumo hospital, was carried out. A total of 227 blood samples of umbillical cord were examined for the presence of their viral antigens such as: Hepatitis B surface antigen (HBsAg), Herpes simplex type 1 and type 2, and anti-rubella IgM as an indicator of early infection due to rubella virus in the fetus. The detection of antigens and anti-rubella IgM in the serum.were done by ELISA methode using reagents which are commercially available. The result of the study indicated that there was a possibility of perinatal infection due to related viruses, i.e.: 2.2%; 1.9% and 14.3% due to HBsAg; Herpes simplex type 1 and type 2 respectivelly, however none of the serum indicated seropositive IgM against rubella virus : infection.


Two processes are necessary to solve group decision making problems: A consensus process and a selection process. The consensus reaching process is necessary to obtain a final solution with a certain level of agreement between the experts; and the selection process is necessary to obtain such a final solution. In a previous paper, we present a selection process to deal with group decision making problems with incomplete fuzzy preference relations, which uses consistency measures to estimate the incomplete fuzzy preference relations. In this paper we present a consensus model. The main novelty of this consensus model is that of being guided by both consensus and consistency measures. Also, the consensus reaching process is guided automatically, without moderator, through both consensus and consistency criteria. To do that, a feedback mechanism is developed to generate advice on how experts should change or complete their preferences in order to reach a solution with high consensus and consistency degrees. In each consensus round, experts are given information on how to change their preferences, and to estimate missing values if their corresponding preference relation is incomplete. Additionally, a consensus and consistency based induced ordered weighted averaging operator to aggregate the experts' preferences is introduced, which can be used in consensus models as well as in selection processes. The main improvement of this consensus model is that it supports the management of incomplete information and it allows to achieve consistent solutions with a great level of agreement.


: The lysozyme gene is expressed at a low level in myeloblasts and is progressively activated to constitutively high expression in mature macrophages. The binding activity of the newly defined NF-kappa B/Rel family of transcription factors increases during the terminal differentiation of macrophages. In this study, I show that NF-kappa B/Rel-like proteins bind to the nuclear factor kappa B (kappa B)-like sequence of the lysozyme promoter. These binding activities were induced by treatment of HD11 cells with lipopolysaccharide. Immunomobility shift assays show that c-Rel is possibly a factor in the complexes that bind to the kappa B-like sequence lys kappa B. Binding activity to one of the protein complexes seems to be regulated by phosphorylation. In fact, overexpression of p65 and c-Rel stimulates expression of the chloramphenicol acetyltransferase gene controlled by the lysozyme promoter. Furthermore, co-transfection experiments reveal that the kappa B-like sequence within the lysozyme promoter mediates the transactivation by p65 and c-Rel. These results indicate that the p65 and c-Rel could be components of the protein complexes that bind to the kappa B-like sequence and this binding could contribute to the progressively activated expression of the lysozyme gene during the terminal differentiation of macrophages.


Pyridoxal 5′-phosphate (PLP) is an important cofactor for amino acid decarboxylases with many biological functions, including the synthesis of signalling molecules, such as serotonin, dopamine, histamine, γ-aminobutyric acid, and taurine. Taurine is an abundant amino acid with multiple physiological functions, including osmoregulation, pH regulation, antioxidative protection, and neuromodulation. In mammalian tissues, taurine is mainly produced by decarboxylation of cysteine sulphinic acid to hypotaurine, catalysed by the PLP-dependent cysteine sulphinic acid decarboxylase (CSAD), followed by non-enzymatic oxidation of the product to taurine. We determined the crystal structure of mouse CSAD and compared it to other PLP-dependent decarboxylases in order to identify determinants of substrate specificity and catalytic activity. Recognition of the substrate involves distinct side chains forming the substrate-binding cavity. In addition, the backbone conformation of a buried active-site loop appears to be a critical determinant for substrate side chain binding in PLP-dependent decarboxylases. Phe94 was predicted to affect substrate specificity, and its mutation to serine altered both the catalytic properties of CSAD and its stability. Using small-angle X-ray scattering, we further showed that similarly to its closest homologue, GADL1, CSAD presents open/close motions in solution. The structure of apo-CSAD indicates that the active site gets more ordered upon internal aldimine formation. Taken together, the results highlight details of substrate recognition in PLP-dependent decarboxylases and provide starting points for structure-based inhibitor design with the aim of affecting the biosynthesis of taurine and other abundant amino acid metabolites.


: The ATP: L-methionine-S-adenosyltransferase of rat cerebral cortex and cerebellum was found to be differentially responsive to solubilization by sodium deoxycholate. Furthermore, the cerebellar enzyme was markedly less sensitive to inactivation by deoxycholate and to storage at 4 degrees C. The specific activity of the cerebellar enzyme was significantly higher and the two enzyme activities also exhibited differences in apparent Km values for L-methionine.


The concept of sustainability has been considered as a framework for understanding the development process and environment resource management as well as delicate a balance between economy, environment and health sociality around the world in the recent decades. This research tries to determine the level of sustainability of Karaj rural development in order to identify and investigate the possibilities of Karaj County. For this purpose, 30 indicators of social, economic and environmental and structural-infrastructural are applied, using factor analysis and cluster analysis techniques for grading and evaluating the sustainability of the 82 villages were used in Karaj County. Thus, the 30 variables were reduced to 4 factors. According to the result of the principal component analysis with rotation, 65.32% of total variance among the 30 variables was explained by these 4 factors. Results indicate undesirable present condition in the studied region which Farokh Abad and Ghezel Hesar villages are sustainable, while Morad Abad and Ahmad Abad villages are unsustainable comparison with other settlements. Finally, the strategy policies are presented in different dimension in order to enhance and improve of the sustainability of Karaj County.


AORTICOINTESTINAL fistula is now a well-recognized complication following abdominal aortic grafting. Sepsis is frequently an associated feature of this catastrophe, and successful management of the problem continues to challenge the ingenuity of the vascular surgeon. The vast majority of these communications develop between the graft and the duodenum, the jejunum and ileum being less frequently involved. 1 We were unable to discover any reported instances of graft rupture into the colon, although undoubtedly, there have been unreported cases. The following case is presented as an example of aorticosigmoid fistulization and sepsis following the insertion of a knitted Dacron bifurcation graft. Our attempt to manage this patient without restoring aortic continuity met with prompt and unqualified failure. We feel that the unique clinical features associated with rupture at this unusual site and our experiences in dealing with this patient are worthy of report. Report of Case A 69-year-old man was first


The family, not only the coach, plays a major role in the pursuit of children to reach the highest level in sport. Yet, it is mainly the high achiever, and sometimes the coach, who get recognition for success in this regard. This study explored the experiences of families with high-achieving adolescent athletes aspiring to compete in the Olympics. The participants consisted of three purposively selected South African families. In-depth phenomenological interviews were conducted. Data were analysed by means of thematic coding. Four themes were identified: a child who is an achiever in sport affects the whole family; acceptance of the trying circumstances of being a high achiever in sport made it easier for the achiever child to cope; as siblings grow older, they try to find their own niche in the family; and coaches become as important to children as their own parents. A cross-validation report of the three case studies and a discussion of findings in the literature give insight into an understanding of the everyday lives of high achievers in sport.


The presence of multiple concurrent infections, or polyparasitism, is quite common in schistosomiasis endemic areas. Msambweni District in the Coast Province of Kenya is highly endemic for Schistosoma haematobium. Previous studies showed an overall prevalence of schistosomiasis in Msambweni District at 40% to 60%. This is a prevalence way above the national prevalence of approximately 23%. There has been continued support by various agencies, including the government and non-governmental organizations (NGO's) in providing treatment and control of the disease in the area. However, the long term impact of these programs in the reduction of the overall prevalence of the disease has not been fully evaluated. This survey of 1232 people aged 5-78 years in two villages in Vingujini Sub-Location Msambweni District of Coast Province, Kenya was conducted to determine prevalence of Schistosoma haematobium and soil transmitted helminthes infections. Urine and stool samples were collected and examined for eggs of Schistosoma haematobium and intestinal helminthes. Haematuria was determined using urine dip strips. Hemoglobin levels were determined to establish the relationship between the intensity of hookworm disease and anemia. The overall occurrence of parasitic infections were, 43.99% for Schistosoma haematobium, 29.63% for hookworm disease, 0.49% for ascariasis and 24.59% for trichuriasis (N=1232). Only 32.71% were free from any of the parasitic infections screened. Age was related to infection with schistosomiasis (f=95.17, p>0.01), hookworm disease (f=11.51, p= 0.010) and trichuriasis (f=26.46, p>0.01). Infection with Schistosomiasis was highly correlated with Trichuris infection (r=0.96, p=0.006). Intensities of Schistosomiasis and hookworm were highly related to age (p<0.01). High intensities of Schistosoma haematobium were associated with haematuria (f=639.99, p<0.01). Intensity with hookworm was correlated to anemia (r=-0.091, p<0.01). Individuals with heavy and light infections were more likely to suffer from anemia than individuals with low intensities or the non-infected (f=5.5, p<0.01). The results of this study have shown that the problem of urinary schistosomiasis and soil transmitted helminthes persists despite the control programs and enhancement of these control programs is required.


Abstract : Complex systems, such as manufacturing supply chains, are often modeled as a collection of interacting components with information flows between them. These components are frequently responsible for making a wide range of decisions that are implemented using an optimization, heuristic, or control technique. The traditional approach to system performance focuses on the performance of these components. The view has been that to improve the system performance one had only to develop better techniques. In this paper, we argue that inadequate attention has been paid to the relationship between information and system performance. Information has played an important role in the manufacturing systems of the past. It will play a dominant role in the Internet-based manufacturing systems of the future. To better design, engineer, implement, and control these systems, we need a fundamental understanding of information and its effects on system dynamics. This paper contends that we need a new characterization of information, a delineation of its salient properties, quantitative metrics for those properties, methods for computing these metrics, and linkages between these metrics and system performance. We focus principally on the first of these, a new characterization of information, and discuss the implications of suggested characterizations for metrics and their measurement, suggesting some approaches for further research.


Context. Solar observations suggest that some of the most dynamic active regions are associated with complex photospheric magnetic configurations such as quadrupolar regions, and especially those that have a δ-spot configuration and a strong polarity inversion line (PIL).
Aims. We study the formation and eruption of magnetic flux ropes in quadrupolar regions.
Methods. We performed 3D magnetohydrodynamics simulations of the partial emergence of a highly twisted flux tube from the solar interior into a non-magnetised stratified atmosphere. We introduced a density deficit at two places along the length of the subphotospheric flux tube to emerge as two Ω-shaped loops, forming a quadrupolar region.
Results. At the photosphere, the emerging flux forms two initially separated bipoles, which later come in contact, forming a δ-spot central region. Above the two bipoles, two magnetic lobes expand and interact through a series of current sheets at the interface between them. Two recurrent confined eruptions are produced. In both cases, the reconnection between sheared low-lying field lines forms a flux rope. The reconnection between the two lobes higher in the atmosphere forms field lines that retract down and push against the flux rope, creating a current sheet between them. It also forms field lines that create a third magnetic lobe between the two emerged lobes, that later acts as a strapping field. The flux rope eruptions are triggered when the reconnection between the flux ropes and the field above the ropes becomes efficient enough to remove the tension of the overlying field. These reconnection events occur internally in the quadrupolar system, as the atmosphere is non-magnetised. The flux rope of the first, weaker, eruption almost fully reconnects with the overlying field. The flux rope of the second, more energetic, eruption is confined by the overlying strapping field. During the second eruption, the flux rope is enhanced in size, flux, and twist, similar to confined-flare-to-flux-rope observations. Proxies of the emission reveal the two erupting filaments channels. A flare arcade is only formed in the second eruption owing to the longer lasting and more efficient reconnection at the current sheet below the flux rope.


Atypical enteropathogenic Escherichia coli (aEPEC) strains produce attaching-effacing (AE) lesions on enterocytes due to the interaction of the adhesin intimin with its translocated receptor. aEPEC strain 1551-2 was previously shown to invade HeLa and T84 cells by means of the uncommon intimin subtype omicron. Other aEPEC strains carrying uncommon intimin subtypes have also been shown to invade differentiated T84 intestinal cells. In this study, seven aEPEC strains carrying the most common EPEC intimin subtypes (alpha, beta, and gamma) were evaluated regarding the ability to invade differentiated intestinal Caco-2 cells. Although all strains adhered to and promoted AE lesions, the numbers of cell-associated bacteria varied significantly between the different strains regardless of the intimin subtype (P < 0.05). Gentamicin protection assay and transmission electron microscopy analyses showed that in comparison with the invasive strain 1551-2, only one strain (aEPEC EC423/03, intimin beta) was invasive (P = 0.05). Although both strains persisted intracellularly until 48 h, the number of viable bacteria of EC423/03 decreased, whereas that of 1551-2 increased significantly up to 24 h and then decreased. In conclusion, invasiveness is a sporadic property among aEPEC strains carrying some common intimin subtypes.


Objective To construct a predictive tool for the efficacy of intravenous immunoglobulin (IVIG) therapy in children with Kawasaki disease (KD) in Beijing, China. Design This was a cohort study. Data set (including clinical profiles and laboratory findings) of children with KD diagnosed between 1 January 2010 and 31 December 2015 was used to analyse the risk factors and construct a scoring system. Data set of children with KD diagnosed between 1 January 2016 and 1 December 2016 was used to validate this model. Setting Children's Hospital Capital Institute of Pediatrics and Beijing Children's Hospital. Patients 2102 children diagnosed with KD. Interventions No. Main outcome measures Responsiveness to IVIG. Results The predictive tool included C reactive protein ≥90 mg/L (3 points), neutrophil percentage ≥70% (2.5 points), sodium ion concentration <135 mmol/L (3 points), albumin <35 g/L (2.5 points) and total bilirubin >20 μmol/L (5 points), which generated an area under the the receiver operating characteristic curve of 0.77 (95% CI 0.71 to 0.82) for the internal validation data set, and 0.69 (95% CI 0.58 to 0.81) and 0.63 (95% CI 0.53 to 0.72) for two external validation data sets, respectively. If a total of ≥6 points were considered high-risk for IVIG resistance, sensitivity and specificity were 56% and 79% in the internal verification, and the predictive ability was similar in the external validation. Conclusions The predictive tool is helpful in early screening of high-risk IVIG resistance of KD in the Beijing area. Consequently, it will guide the clinician in selecting appropriate individualised regimens for the initial treatment of this disease, which is important for the prevention of coronary complications.


We analyze an economy where firms undertake both innovation and adoption of technologies from the world technology frontier. The selection of high-skill managers and firms is more important for innovation than for adoption. As the economy approaches the frontier, selection becomes more important. Countries at early stages of development pursue an investment-based strategy, which relies on existing firms and managers to maximize investment but sacrifices selection. Closer to the world technology frontier, economies switch to an innovation-based strategy with short-term relationships, younger firms, less investment, and better selection of firms and managers. We show that relatively backward economies may switch out of the investment-based strategy too soon, so certain policies such as limits on product market competition or investment subsidies, which encourage the investment-based strategy, may be beneficial. However, these policies may have significant long-run costs because they make it more likely that a society will be trapped in the investment-based strategy and fail to converge to the world technology frontier. (JEL: O31, O33, O38, O40, L16)


A housekeeping basolateral Cl- channel in rabbit gastric parietal cells (0.3-0.4 pS) is closed by an intracellular application of GTP gamma S. Here, we found a novel GTP gamma S-dependent regulatory mechanism, in which GTP gamma S stimulates intracellular superoxide (O2-) production and the O2- acts as a messenger in the closure of the Cl- channel. Other oxygen species such as .OH and H2O2 were not involved in the closing mechanism.


ABSTRACT This study aims to establish a visual search scale that measures shoppers' in-store exploration behavior. We propose that the attentional control theory used in the psychology domain is transferable to the marketing domain, thus adding a new perspective to existing models of shoppers' in-store exploration behavior. We develop our psychometric scales and test them over four phases to confirm their validity. Finally, we discuss how visual search could affect shoppers' in-store exploration behavior, giving marketing managers a new way to deliver effective in-store advertisements, encourage shoppers' impulsivity, and improve customer relationship management. Marketing managers and manufacturers can use our visual search scale to easily capture several important aspects: the extent to which shoppers consider a product that they do not plan on buying before entering the store, which product categories tend to be considered impulsively, and if in-store shopping behaviors differ between planned and impulsive considerations.


Abstract. Over the last 40 years, many contributions have identified empirical rainfall thresholds (e.g. rainfall intensity (I) vs. rainfall duration (D), cumulated rainfall vs. rainfall duration (ED), cumulated rainfall vs. rainfall intensity (EI)) for the possible initiation of shallow landslides, based on local and global inventories. Although different methods to trace the threshold curves have been proposed and discussed in literature, a systematic study to develop an automated procedure to select the rainfall event responsible for the landslide occurrence has only rarely been addressed. Objective criteria for estimating the rainfall responsible for the landslide occurrence play a prominent role on the threshold values. In this paper, two criteria for the identification of the effective rainfall events are presented. The first criterion is based on the analysis of the time series of rainfall mean intensity values over 1 month preceding the landslide occurrence. The second criterion is based on the analysis of the trend in the time function of the cumulated mean intensity series calculated from the rainfall records measured through rain gauges. The two criteria have been implemented in an automated procedure that is written in the R language. A sample of 100 shallow landslides collected in Italy from 2002 to 2012 was used to calibrate the procedure. The cumulated event rainfall (E) and duration (D) of rainfall events that triggered the documented landslides are calculated through the new procedure and are fitted with power law in the D, E diagram. The results are discussed by comparing the D, E pairs calculated by the automated procedure and the ones by the expert method.


INTRODUCTION
The Canadian Association of Emergency Physicians (CAEP) published a position statement in 2006 encouraging immediate access to emergency medicine ultrasonography (EMUS) 24 hours a day, 7 days a week. However, barriers to advanced imaging care still exist in many rural hospitals. Our study investigated the current availability of EMUS in rural communities and physicians' ability to use this technology.

METHODS
A literature review and interviews with rural physicians were conducted in the summer of 2010 to design a questionnaire focusing on EMUS. The survey was then sent electronically or via regular mail in November 2010 to all Ontario physicians self-identified as "rural." Descriptive statistics and the Fisher exact test were used to analyze the data.

RESULTS
A total of 207 rural physicians responded to the survey (response rate 28.6%). Of the respondents, 70.9% were male, median age was 49 years and median year of graduation was 1988. The respondents had been in practice for a median of 20 years and had been in their present community for a median of 15 years. More than two-thirds of physicians (69.5%) practised in communities with populations of less than 10 000. Nearly three-quarters (72.6%) worked in a rural emergency department (ED). Almost all (96.9%) reported having access to ultrasonography in the hospital. However, only 60.6% had access to ultrasonography in the ED. Less than half (44.4%) knew how to perform ultrasonography, with 77.3% citing lack of training. Of those using EMUS, 32.5% were using it at least once per shift. The most common reason to use EMUS was to rule out abdominal aortic aneurysm (58.3%). Most respondents (71.5%) agreed or strongly agreed that EMUS is a skill that all rural ED physicians should have.

CONCLUSION
Patients in many rural EDs do not have immediate access to EMUS, as advocated by CAEP. This gap in care needs to be addressed to ensure that all patients, no matter where they live, have access to this proven imaging modality.


Desmoplastic melanoma can be difficult to distinguish from desmoplastic melanocytic nevi both clinically and histopathologically. Several attempts have been made to explore the use of ancillary studies to facilitate this distinction. Prior work has suggested that immunohistochemical expression of p16 could help distinguish sclerosing Spitz nevi from desmoplastic melanomas. We re‐evaluated the expression of p16 in 22 desmoplastic melanomas (13 mixed and 9 pure desmoplastic tumors) and five desmoplastic melanocytic nevi (three desmoplastic Spitz nevi and two congenital melanocytic nevi with prominent dermal sclerosis). All desmoplastic melanocytic nevi were strongly immunoreactive for p16. Of the 22 desmoplastic melanomas, 6 tumors failed to label for p16, 10 were focally positive, but 6 tumors were diffusely immunoreactive. The latter finding is relevant, as it points to limitations in the diagnostic value of immunohistochemical staining for p16 for the diagnosis of desmoplastic melanocytic proliferations. Diffuse staining for p16 is not restricted to desmoplastic Spitz nevi but can also occur in a subset of desmoplastic melanomas, and this warrants caution in the use of this marker for diagnostic purposes.


Thousands of introns have been localized to rRNA genes throughout the three domains of life. The consequences of the presence of either a spliced or an unspliced intron in a rRNA for ribosome assembly and packaging are largely unknown. To help address these questions, and to begin an intron imaging study, we selected a member of the self-splicing group II intron family, which is hypothesized to be the progenitor not only of spliceosomal introns but also of non-LTR retrotransposons. We cloned the self-splicing group II Ll.LtrB intron from Lactococcus lactis into L. lactis 23S rRNA. The 2,492-nt Ll.LtrB intron comprises a catalytic core and an ORF, which encodes a protein, LtrA. LtrA forms a ribonucleoprotein (RNP) complex with the intron RNA to mediate splicing and mobility. The chimeric 23S-intron RNA was shown to be splicing proficient in its native host in the presence of LtrA. Furthermore, a low-resolution cryo-EM reconstruction of the L. lactis ribosome fused to the intron-LtrA RNP of a splicing-defective Ll.LtrB intron was obtained. The image revealed the intron as a large, well defined structure. The activity and structural integrity of the intron indicate not only that it can coexist with the ribosome but also that its presence permits the assembly of a stable ribosome. Additionally, we view our results as a proof of principle that ribosome chimeras may be generally useful for studying a wide variety of structured RNAs and RNP complexes that are not amenable to NMR, crystallographic, or single-particle cryo-EM methodologies.


How to improve generative modeling by better exploiting spatial regularities and coherence in images? We introduce a novel neural network for building image generators (decoders) and apply it to variational autoencoders (VAEs). In our spatial dependency networks (SDNs), feature maps at each level of a deep neural net are computed in a spatially coherent way, using a sequential gating-based mechanism that distributes contextual information across 2-D space. We show that augmenting the decoder of a hierarchical VAE by spatial dependency layers considerably improves density estimation over baseline convolutional architectures and the state-of-the-art among the models within the same class. Furthermore, we demonstrate that SDN can be applied to large images by synthesizing samples of high quality and coherence. In a vanilla VAE setting, we find that a powerful SDN decoder also improves learning disentangled representations, indicating that neural architectures play an important role in this task. Our results suggest favoring spatial dependency over convolutional layers in various VAE settings. The accompanying source code is given at https://github.com/djordjemila/sdn.


Community health centers are non-profit, community-oriented healthcare providers. Generally, they are a subset of Federally Qualified Health Centers, institutions that receive special funding because they provide medical care to underserved populations. They offer preventative and primary healthcare, including physical exams, routine testing and screening, immunizations, dental care, pediatrics, women's health, prenatal care, and nutritional services. These clinics are open to all, but designed to reach out to underserved populations, especially low-income individuals, racial and ethnic minorities, recent immigrants, and rural populations. The National Association of Community Health Centers estimates that nationally, their clinics provide health services for over 23 million people, and this number is increasing. To give one example from Buffalo, the Jericho Road Family Practice serves more than 30,000 people each year.


Currently there are more than 51.2 million people forcibly displaced worldwide (UNHCR 2014), with women and their dependent children comprising approximately 70–75 percent of the world's displaced population. Through a critical, feminist reading of citizenship and social inclusion following scholars such as Ruth Lister, Iris Marion Young, Gayatri Spivak, Chandra Talpade Mohanty, bell hooks, and Chantal Mouffe, this paper explores a qualitative research study of how a small group of Sierra Leonean refugee women resettling in Sydney, Australia experience educational access and family protection before, during, and after forced migration. Drawing upon the participants' narrative accounts, this paper investigates the complex human rights challenges faced by women who are socially positioned as subaltern and as refugees. Their voices depict how certain groups of women may be excluded from the "universal" human rights of education and family protection as outlined in the principal human rights document, The Universal Declaration of Human Rights (United Nations 2015). It is argued that in order to advance human rights culture and democratic participation in civil society the voices and experiences of subaltern women refugees and forced migrants must be centred in the construction of knowledge about the complex social factors leading up to forced migration and the actualities of refugee resettlement.


Efforts to improve retention in science, technology, engineering, and mathematics (STEM) majors frequently utilize peer mentors and/or leaders. At Authors' University, the STEM Ambassador (SA) program involves students in the creation of a STEM community through multifaceted roles as mentors, peer-learning facilitators, and social organizers. The program utilizes best practices in organizational leadership and leadership development to maximize the effectiveness of the SAs. The program has resulted in positive perceptions of the SAs, increased retention of STEM students that participate in the SA-led activities, and a well nurtured, professionally developed set of students that serve as SAs.


Serum aluminium concentrations and biopsy specimens of bone were examined in 56 patients with end stage chronic renal failure receiving maintenance haemodialysis. Deposits of aluminium in bone specimens were often associated with low bone formation with or without osteomalacia. Serum aluminium concentrations of greater than 3.7 mumol/l (10 micrograms/100 ml) indicated a high probability of deposits of aluminium in bone specimens, although high serum concentrations did not predict the type of renal bone disease. Biopsy of the bone is the best method of detecting aluminium intoxication of bone. A serum aluminium concentration of 3.7 mumol/l should be the threshold beyond which bone biopsy should be performed to confirm an overload of aluminium and identify histological bone changes induced by aluminium.


We have designed an agent-based architecture for quantitative service provisioning in differentiated services capable networks. For each link-state routing domain in the network there is a topology-aware QoS agent (also known as a bandwidth broker) responsible for admission control. The architecture provides resource reservations for aggregated virtual leased lines between network domains. In this paper, we present performance measurements for resource provisioning in a prototype QoS agent. This includes an evaluation of two data structures for advance reservations and accompanying algorithms. We also compare the cost for on-demand route computations with pre-computation of routes. The objective in this paper is to evaluate the performance of end-to-end admission control within a single link-state routing domain. In a domain with 15 routers, 28 transition networks and 64 stub networks, our prototype performs approximately 25000 end-to-end admission decisions per second. The results show that an ordinary PC can be used for running a QoS agent that performs path-sensitive admission control and maintains per link resource reservations in a link-state routing domain.


This paper concerns the investigation of the stresses, displacement and temperature due to the axisymmetric thermal shock loading on the inner boundary in a transversely isotropic thin annular disc. The analysis encompasses thermo-elasticity without energy dissipation theory (TEWOED (GNII)) and three-phase-lag theory of the generalized thermo-elasticity to account for the finite velocity of the temperature. The Laplace transform method is used to transform the coupled equations into the space domain, where two different methods, eigen-value approach and the Galerkin finite element technique are employed to solve the resulting equations in the transformed domain. The inverse of the transformed solution is carried out by applying a method of Bellman et al. Stresses, displacement and temperature distributions have been computed numerically and presented graphically in a number of figures. A comparison of the results for different theories (GN-II and Three-phase-lag model) and for two different methods are presented.


Cardiovascular diseases (CVDs) are the leading cause of mortality and a major economic burden worldwide. Various drugs, including antihypertensive, antihyperlipidemic, and antiplatelet agents, are prescribed to treat CVDs, but these agents have side effects, includ - ing serious side effects such as bleeding. Therefore, efforts are being made to develop new drugs made of natural substances with relatively weak side effects. Essential oils are natural substances extracted from aromatic plants with biological effects, such as antioxi dant and antiinflammatory activities. These oils have therefore long been used in tradi - tional medicines. This chapter reviews the effects of essential oils on CVD-related factors. Essential oils have various effects, including improvements in lipid balance, liver func - tion, and endothelial function; reductions in blood pressure, oxidative stress, thrombosis, and inflammation; promotion of vascular relaxation; and inhibition of diabetes devel - opment and angiogenesis. Therefore, essential oils and their active components may be promising therapeutic agents for CVDs. Further studies are needed to clarify their clini- cal effects and to elucidate their specific mechanisms of activity.


Objective: Hyperimmunoglobulin M (HIGM) syndromes are primary immunodeficiencies characterized by normal or elevated serum IgM levels with decreased levels of other immunoglobulin isotypes. Over the past decade rapid progress has been made in the molecular and genetic basis of HIGM and five distinct subgroups have been described. Materials and Methods: Records of patients diagnosed as HIGM were retrospectively reviewed to describe the demographic characteristics, initial clinical presentation, age at onset and diagnosis and family history of immunodeficiency, in addition to basic immunological laboratory parameters, and information about follow-up and outcome of patients. Laboratory analyses included complete blood cell and differentials, serum immunoglobulin levels and immunophenotyping of peripheral blood lymphocytes. Flow cytometric analyses of CD40 and stimulated CD40 ligand (CD40L) expression were performed and compared to healthy controls. Results: We hereby describe 5 HIGM cases (1 female, 4 male) followed in our unit with a mean duration of 7.2 (median 9 years; min-max: 0.4-11.6) years. The age at diagnosis ranged between 1.3-2.3 years (median 2 years), whereas onset of symptoms was generally during infancy. Four cases were from consanguineous parents. Neither autoimmunity, lymphoma, neutropenia or ectodermal dysplasia were detected in any of cases. Evaluation of CD40 was available in four cases and showed normal expression. Stimulated CD40L expressions were found to be normal in the girl and remarkably lower than healthy controls in three boys. Lung imaging revealed bronchiectasis in three patients. All patients are under intravenous immunoglobulin treatment and antibiotic prophylaxis. Conclusion: HIGM is associated with an increased risk of severe infections and chronic lung damage. Early-diagnosis and prompt initiation of intravenous immunoglobulin therapy is essential to prevent complications.


We calculate the current-voltage characteristics and critical current I_c^{array} of an array of Josephson-coupled superconducting wires. The array has two layers, each consisting of a set of parallel wires, arranged at right angles, such that an overdamped resistively-shunted junction forms wherever two wires cross. A uniform magnetic field equal to f flux quanta per plaquette is applied perpendicular to the layers. If f = p/q, where p and q are mutually prime integers, I_c^{array}(f) is found to have sharp peaks when q is a small integer. To an excellent approximation, it is found in a square array of n^2 plaquettes, that I_c^{array}(f) \propto (n/q)^{1/2} for sufficiently large n. This result is interpreted in terms of the commensurability between the array and the assumed q \times q unit cell of the ground state vortex lattice.


The green microalga Lobosphaera incisa accumulates triacylglycerols (TAGs) with exceptionally high levels of long-chain polyunsaturated fatty acid (LC-PUFA) arachidonic acid (ARA) under nitrogen (N) deprivation. Phosphorous (P) deprivation induces milder changes in fatty acid composition, cell ultrastructure, and growth performance. We hypothesized that the resource-demanding biosynthesis and sequestration of ARA-rich TAG in lipid droplets (LDs) are associated with the enhancement of catabolic processes, including membrane lipid turnover and autophagic activity. Although this work focuses mainly on N deprivation, a comparative analysis of N and P deprivation responses is included. The results of lipidomic profiling showed a differential impact of N and P deprivation on the reorganization of glycerolipids. The formation of TAG under N deprivation was associated with the enhanced breakdown of chloroplast glycerolipids and the formation of lyso-lipids. N-deprived cells displayed a profound reorganization of cell ultrastructure, including internalization of cellular material into autophagic vacuoles, concomitant with the formation of LDs, while P-deprived cells showed better cellular ultrastructural integrity. The expression of the hallmark autophagy protein ATG8 and the major lipid droplet protein (MLDP) genes were coordinately upregulated, but to different extents under either N or P deprivation. The expression of the Δ5-desaturase gene, involved in the final step of ARA biosynthesis, was coordinated with ATG8 and MLDP, exclusively under N deprivation. Concanamycin A, the inhibitor of vacuolar proteolysis and autophagic flux, suppressed growth and enhanced levels of ATG8 and TAG in N-replete cells. The proportions of ARA in TAG decreased with a concomitant increase in oleic acid under both N-replete and N-deprived conditions. The photosynthetic apparatus's recovery from N deprivation was impaired in the presence of the inhibitor, along with the delayed LD degradation. The GFP-ATG8 processing assay showed the release of free GFP in N-replete and N-deprived cells, supporting the existence of autophagic flux. This study provides the first insight into the homeostatic role of autophagy in L. incisa and points to a possible metabolic link between autophagy and ARA-rich TAG biosynthesis.


The CDIO initiative aims at reforming the classical way engineering is being
taught at technical universities. However, current teaching staff often feels
resistance to making changes to a style of teaching that they themselves
experienced as students. Due to ignorance about the results of research in
higher education, they know little about the implications of the classical
teaching culture in engineering on student's learning.
This paper uses commonly accepted research findings to analyse the consequences
of the classical teaching culture at a typical department of computer science.
It is meant to provoke a pedagogical discussion and to increase the awareness
about pedagogical questions at engineering departments that have not yet turned
to the CDIO initiative.


Neurophysiological studies of sleep have increasingly focused on underlying dynamic processes. This would appear particularly relevant to the developmental aspects of sleep. Involvement of sleep‐dependent mechanisms in emotional processing, as well as perceptual‐sensory, perceptual‐motor, and cognitive learning, mostly studied in adults, may play major roles in development. Rapid eye movement (REM) sleep, which is generated by complex neuronal interactions within the pontine reticular formation, and non‐REM sleep, which arises from activities in the thalamocortical network, are specifically implicated in different aspects of long‐term memory systems. They evolve from previous physiological and behavioural states which can be traced back to the fetal period. Further studies are needed to clearly identify functions reflected by hallmarks of sleep stages, such as spindles and K complexes. A better understanding of the maturational aspects of sleep should provide important insights into physiological development. Assessment approaches taking dynamic characteristics of sleep into account may contribute to the design of better targeted management of sleep‐related problems in neurodevelopmental conditions.