Transforming growth factor-beta (TGF-beta) is a proinvasive and immunosuppressive cytokine that plays a major role in the malignant phenotype of gliomas. One novel strategy of disabling TGF-beta activity in gliomas is to disrupt the signaling cascade at the level of the TGF-beta receptor I (TGF-betaRI) kinase, thus abrogating TGF-beta-mediated invasiveness and immune suppression. SX-007, an orally active, small-molecule TGF-betaRI kinase inhibitor, was evaluated for its therapeutic potential in cell culture and in an in vivo glioma model. The syngeneic, orthotopic glioma model SMA-560 was used to evaluate the efficacy of SX-007. Cells were implanted into the striatum of VM/Dk mice. Dosing began three days after implantation and continued until the end of the study. Efficacy was established by assessing survival benefit. SX-007 dosed at 20 mg/kg p.o. once daily (q.d.) modulated TGF-beta signaling in the tumor and improved the median survival. Strikingly, approximately 25% of the treated animals were disease-free at the end of the study. Increasing the dose to 40 mg/kg q.d. or 20 mg/kg twice daily did not further improve efficacy. The data suggest that SX-007 can exert a therapeutic effect by reducing TGF-beta-mediated invasion and reversing immune suppression. SX-007 modulates the TGF-beta signaling pathway and is associated with improved survival in this glioma model. Survival benefit is due to reduced tumor invasion and reversal of TGF-beta-mediated immune suppression, allowing for rejection of the tumor. Together, these results suggest that treatment with a TGF-betaRI inhibitor may be useful in the treatment of glioblastoma.


In search for matrix proteins released from secretory vesicles of human neutrophils, a prominent 67-kD protein was identified in the extracellular medium of neutrophils stimulated by the chemotactic peptide, FMLP. The protein was purified to apparent homogeneity and partially sequenced. The sequence of the first 32 NH2-terminal amino acids was identical to the sequence of albumin. mRNA for human albumin could not be detected in bone marrow cells, nor could biosynthetic labeling of albumin be demonstrated in bone marrow cells during incubation with [14C]leucine. Immunofluorescence studies on single cells demonstrated the presence of intracellular albumin in fixed permeabilized neutrophils. Light microscopy of immunogold-silver-stained cryosections visualized albumin in cytoplasmic "granules." The morphology of these was determined by immunoelectron microscopy as vesicles of varying form and size. Subcellular fractionation studies on unstimulated neutrophils demonstrated the presence of albumin in the low density pre-gamma and gamma-regions that contain secretory vesicles, but are devoid of specific granules and azurophil granules. Albumin was readily released from these structures during activation of neutrophils with inflammatory mediators. Immunoblotting demonstrated the presence of immunoglobulin and transferrin along with albumin in exocytosed material from stimulated neutrophils. This indicates that secretory vesicles are unique endocytic vesicles that can be triggered to exocytose by inflammatory stimuli.


A type 17-4PH stainless steel tube exhibited brown discoloration after a pickling operation. EDS analysis of the extracted substance revealed relatively high levels of iron and chromium, along with lower amounts of aluminum, silicon, sulfur, chlorine, calcium, manganese, and nickel. The iron, chromium, and nickel are likely in the form of dissolution products from the pickling solution. FTIR analysis revealed the presence of polypropylene and poly(ethylene:propylene). The EDS results showed that the discoloration of the tube was associated with oxidation products of the tube material, as well as adherent organic residue. Analysis by FTIR of the residue revealed detectable levels of two polymeric substances, which were later determined to be construction materials of the pickling tank. It was recommended that more frequent cleaning and/or replacement of the pickling solution be put into place and another type of tank material be considered.


The purpose of this study was to determine whether the inheritance of psoriasis is HLA linked. We studied 12 families with at least two siblings with psoriasis. We used a sib pair analysis comparing the HLA haplotypes in affected siblings of these families. Haplotype sharing was analyzed in 15 sib pairs; expected frequencies of haplotype sharing were estimated as 25% for HLA identity and 50% for haplotype identity. All sib pairs shared at least one haplotype and 13 of the 15 were HLA identical, compared with the expected frequency of four. These results suggest that at least one, and probably more, HLA-linked genes are implicated in the development of psoriasis.


The recently discovered scleractinian coral Tethocyathus endesa (Cairns, Haussermann and Forsterra, 2005) is a cold-water coral, thriving in the fjord Comau (Chile). It exhibits horizontal and vertical pH gradients resembling values forecasted for the end of this century by the recent IPCC-report (IPCC, 2014). Ongoing ocean acidification and global ocean warming might have harmful impacts on all calcifying organisms such as scleractinians. This study aims for a better understanding of the metabolic response of T. endesa in a changing ocean. Measured parameters were in situ growth rates and respiration rates as being two of the main factors that can be influenced by ocean acidification. In 2014, test corals were placed at two study sites (inside the fjord with low pH of 7.67 ± 0.05 and outside the fjord with higher pH of 7.87 ± 0.06). For each study site, ten specimens of T. endesa stayed at their place of origin to determine the general in situ long-term growth rates (one year) as well as to serve as a control for a cross- transplantation experiment. For the latter, additional ten specimens of T. endesa were exchanged to the other study site in 2014. One year later, growth rates were determined via buoyant weighing and respiration rates measured with the aid of optodes. So far there is only little knowledge about the in situ long-term growth rates and the respiration rates of cold-water corals. To the best of our knowledge this is the first study on the reaction of T. endesa towards a changing seawater pH. The findings of this study are therefore crucial to rate the ecological importance of T. endesa and its response to future conditions


Objective: This study was evaluated the ability of Nano hydroxyapatite (nano-HAP) to remineralize the demineralized enamel layer around the orthodontic brackets. Materials and Methods: This study was done on thirty sound freshly extracted permenant premolars. 3M-Unitek brackets were bonded to the buccal surfaces of all specimens. The specimens were artificially demineralized and randomly classified into 3 equal groups A, B and C. They were immersed in artificial saliva for 10days and during this period, group B was treated with 20% nano-HAP varnish, group C was treated with 3%nano-HAP +0.145%sodium fluoride(NaF) paste, while group A was the control group. Selected specimens of each group were scanned by scanning electron microscope (SEM) and assessed by energy dispersive x-ray analysis(EDAX) before and after remineralization, then all samples were subjected to enamel color changes assessment by spectrophotometer and surface roughness assessment by profilometer. The results were statistically analyzed. Significance of the results was set at 0.05. Results: Showed that there were significant increase (P<0.001) in both Calcium and Phosphorus levels after remineralization by nano-HAP. This was detected by EDAX and confirmed by SEM. There was a significant improvement in the color measurements after application of nano-HAP in the study groups when compared to the control group (P<0.001), also the surface roughness has significantly decreased (P<0.001). Conclusion: The findings of our study indicated that nano-HAP with the used protocol in this study could be effective in repairing the demineralized enamel around the orthodontic brackets, restoringthe enamel surface smoothness and its color.


As a new lightweight material and new technique,Tailor Rolled Blanks has a good prospect in energy-saving environmental protection and the future development of the automobile industry, formability window of Tailor Rolled Blanks at blank-holder force has important practical significance. Based on the research of a square box TRB, the paper proposes a theory of TRB' formability window, also with the usage of an ABACUS finite element software to simulate the TRB sheet in the course of the critical wrinkling BHF curve and critical fracture BHF curve, to establish TRB formability window under the condition of blank holder force. The results not only show that the square box of TRB has the security zone in the deep drawing process, but also has got the wrinkling and fracture areas of the square box.


Since immune privilege is believed to exist in the eye in order to suppress sight-destroying inflammation, we wondered whether eyes with intraocular inflammation retain the immune privileged state. Intraocular inflammation was induced by injection of lipopolysaccharide (LPS) into the vitreous cavity of BALB/c mouse eyes, which showed a peak in intensity at approximately 9 h. At this time point, inflamed eyes were examined for their capacity to afford immune privilege to injected allogeneic tumor cells, and to promote anterior chamber-associated immune deviation (ACAID) to antigens injected locally. In addition, aqueous humor (AqH) harvested from inflamed eyes was tested for its ability to suppress T cell activation. Surprisingly, eyes with acute, intense intraocular inflammation allowed allogeneic tumor cells to form progressively growing tumors, and these same eyes promoted ACAID. Moreover, AqH harvested from inflamed eyes strongly inhibited T cell activation. We conclude that the type of extreme, intraocular inflammation evoked by intravitreally injected LPS fails to abolish immune privilege in the eye. These findings are discussed in light of the effects of other types of inflammation on the integrity of ocular immune privilege, and with respect to the capacity of the eye to maintain immune privilege by more than one mechanism.


The cellular fatty acid composition of 10 isolates of symbiotic cyanobacteria from 7 different species of the aquatic fern Azolla was investigated. Sixteen major components accounted for 88.31% of total fatty acids: the saturated 14:0, 16:0 and 18:0 carbon chains; the unsaturated straight-chained 12:1, 14:1 cis-7, 16:1 cis-7, 16:1 cis-9, 16:1 cis-11, 18:2 cis-9, 18:3 cis-9, 18:1 cis- and trans-9, and 20:4 cis-5; and the branch-chained iso-16:0. Also included was an unsaturated 16-carbon (equivalent carbon chain length of 15.5), with unsaturation sites undetermined. The most abundant component was the 16:0 (mean of 38.10% of the total). Thirty-six minor fatty acids, comprising 10.30% of the total, were detected and identified. These included hydroxy-substituted fatty acids (1.10%), branched chains in addition to the iso-16:0 (1.96% of a class total of 2.96%) and cyclopropane fatty acids (0.89%). A comparison of the fatty acid profile of Azolla cyanobionts with those previously published for free-living cyanobacteria of the genera Anabaena and Nostoc indicated that there were at least 19 individual fatty acids, class totals or ratios that were statistically different and could be used as differentiating factors. Nine of the 19 factors were characteristically unique to Azolla cyanobionts and different from both Anabaena and Nostoc. Five were different from only Anabaena, and five from only Nostoc. Based on one taxonomic interpretation of fatty acid analysis, the Azolla cyanobionts appeared to be equally distinct from Anabaena and from Nostoc.


Abstract Megaloptera is a small order of insects that is very rare in the fossil record. Jurochauliodes ponomarenkoi n. gen. n. sp. belonging to Chauliodinae (fishflies) within Corydalidae is described based on three larvae preserved in tuffaceous siltstones from the Middle Jurassic of Daohugou, China. It is not only the first fossil Megaloptera from China, but also the earliest Corydalidae. It differs from Cretochaulus lacustris Ponomarenko, 1976 in having a large body, head much longer than mandibles, mandibles wide, with a small apical tooth, meso- and metathorax half as long as prothorax, profemora apically widened, abdominal segment IX short, and lateral gills shorter than hind legs. This discovery indicates that fishflies originated at least in the Middle Jurassic.


While many-core accelerator architectures, such as today's Graphics Processing Units (GPUs), offer orders of magnitude more raw computing power than contemporary CPUs, their massive parallelism often produces complex dynamic behaviors even with the simplest applications. Using a fixed set of hardware or simulator performance counters to quantify behavior over a large interval of time such as an entire application execution run or program phase may not capture this behavior. Software and/or hardware designers may consequently miss out on opportunities to optimize for better performance. Similarly, significant effort may be expended to find metrics that explain anomalous behavior in architecture design studies. Moreover, the increasing complexity of applications developed for today's GPU has created additional difficulties for software developers when attempting to identify bottlenecks of an application for optimization. This paper presents a novel GPU performance visualization tool, AerialVision, to address these two problems. It interfaces with the GPGPU-Sim simulator to capture and visualize the dynamic behavior of a GPU architecture throughout an application run. Similar to existing performance analysis tools for CPUs, it can annotate individual lines of source code with performance statistics to simplify the bottleneck identification process. To provide further insight, AerialVision introduces a novel methodology to relate pathological dynamic architectural behaviors resulting in performance loss with the part of the source code that is responsible. By rapidly providing insight into complex dynamic behavior, AerialVision enables research on improving many-core accelerator architectures and will help ensure applications written for these architectures reach their full performance potential.


The collapsing layer structure of hydrogen phosphate intercalated Mg/Al-layered double hydroxides (LDH-HPO4) was investigated by high temperature in-situ X-ray diffraction with synchrotron radiation (in-situ XRD). The thermal behavior of the layer structure of LDH-HPO4 showed the same behavior in both in-situ and ex-situ XRD up until 109 °C as previously reported. The basal spacing of LDH-HPO4 continuously decreases above this temperature and finally the layer structure of LDH-HPO4 collapses. Another diffraction peak, d110, which gives a lattice constant a0, decreases at 62 °C, keeps constant to 120°C, increases up to 176°C and again keeps constant until the layer collapse. In this study, the different thermal behavior is observed between two reflections by in-situ XRD measurement, which explains the mechanism of the collapse of the layer structure in LDH-HPO4.


Applying information system technology to business processes is one of the strategies to overcome about problems in data accuration, sales, purchases and making report transactions. By implementing the system, information has resulted at decreased in time transaction and accuracy of the sales, purchase and report making processes. The application of information system technology starts in analysis, design, implementation, testing and maintenance according to the waterfall method. Each stage has a different resolution and function, but is interrelated between one and the other generated by computer applications that can be used in
the business of the company CV. Saragih 3 Brothers


The AA3003 alloy is widely used as fin material in heat exchangers. The life time of these heat exchangers is mostly determined by their corrosion properties. Twin roll casting (TRC) of AA3003 material is known to often result in the formation of a macrosegregation area of alloying elements towards the centre plane of the casted strip (centre line segregation = CLS). Considering the potential exposure of cross-sectional areas of TRC material in the heat exchanger fin application, and the relatively high corrosion susceptibility of the CLS, the study of this region is of key importance to understand the microstructural effects on the resulting corrosion mechanisms and kinetics for these materials. Typically the alloys are homogenized to bring the microstructures closer to an equilibrium state, but the impact of this heat treatment on the corrosion properties is insufficiently studied. Therefore, this study investigates the effect of different homogenization procedures on the corrosion properties of the CLS and the interaction of the intermetallic particles with the surrounding aluminium matrix. This work shows that the pitting corrosion resistance is greatly dependent on the homogenization temperature, with better corrosion resistance obtained with higher temperature, especially near the CLS. This difference in corrosion behaviour is completely attributed to a difference in microstructure and not to an oxide layer effect. Furthermore, it is observed that not only temperature will have a large influence on the corrosion resistance, but duration of the heat treatment as well.


In this paper we present real-time neurocontrol system for a nonlinear dynamic plant. In order to improve the training and control performance we present a combined system with a neurocontroller (NC) and a linear quadratic regulator (LQR). We apply the control scheme to the backward control of a multi-trailer system. The function of the LQR is to cater for the linear part of the system thereby alleviating the load on the NC. An emulator of the plant is used to design the desired trajectory. The actual plant is subsequently run on this path. In the event that the plant fails to trace the desired trajectory, the control system is re-designed from this point and a new trajectory formulated. We utilize the GA to update the NC weights, while the evaluation function of the NC incorporates both the squared errors and the running steps errors; the latter having the function of realizing faster training of the NC. We have significantly reduced the computation time by utilizing one pattern training for the NCs in real time. Simulations show that the proposed online method has good control performance for the trailer truck system.


The ability to do indirectness, inexplicitness and vagueness is a key component in the repertoire of all competent discoursers and these are commonplace phenomena in written and spoken discourses, particularly in conversations. The study reported in the paper seeks to delineate and exemplify these three terms which are used frequently in the literature, but which are potentially confusing as they are not always unambiguously defined and consistently applied. The purpose of the study is to describe the differences between the three terms in terms of their pragmatic usage and functions, drawing upon a corpus of naturally-occurring conversational data between Hong Kong Chinese and native speakers of English. In so doing, this study underlines the widespread occurrence of these forms of language use and the ways in which participants in spoken discourse employ them to jointly construct both context and meaning.


Flight activity recorders have recently confirmed that alpine and common swifts spend the majority of their non-breeding period on the wing, which may last 6–10 months. Here we test the hypothesis that the closely related pallid swift, a species with a breeding distribution around the Mediterranean, lead a similar aerial life-style during its migration and wintering periods. The pallid swift usually lays two clutches in one season and therefore spends more time in the breeding area than the common swift. We successfully tracked four pallid swifts with data loggers that record light for geolocation and acceleration every 5 min to monitor flight activity. The birds wintered south of the Sahel in west Africa from the Ivory Coast to Cameroon. The pallid swifts spent the majority of their non-breeding time in flight, especially the first two months after leaving the breeding area in autumn, while a few landing events occurred during the winter. The total time grounded was < 1%, similar to that of the common and alpine swifts. The mass specific flight metabolic rate of swifts is similar to the average non-breeding metabolic rate of a long distance terrestrial migrant, suggesting swifts are not more likely to procure oxidative damage as a consequence of continuous flight than other migrants. The open airspace used by swifts may provide a relatively safe habitat that explain the high survival rate found in swifts.


The key assumption in regression discontinuity analysis is that the distribution of potential outcomes varies smoothly with the running variable around the cutoff. In many empirical contexts, however, this assumption is not credible; and the running variable is said to be
 manipulated in this case. In this paper, we show that while causal effects are not point identified under manipulation, one can derive sharp bounds under a general model that covers a wide range of empirical patterns. The extent of manipulation, which determines the width of the bounds, is inferred from the data in our setup. Our approach therefore does not require making a binary decision regarding whether manipulation occurs or not, and can be used to deliver manipulation‐robust inference in settings where manipulation is conceivable, but not obvious from the data. We use our methods to study the disincentive effect of unemployment insurance on (formal) reemployment in Brazil, and show that our bounds remain informative, despite the fact that manipulation has a sizable effect on our estimates of causal parameters.


Background An interaction of the food types with the gut microbiota changes is deeply implicated in human health and disease. To verify whether animal-based diets would lead to gut dysbiosis, systemic inflammation and inflammatory pathogenesis, we fed mice with chondroitin sulfate (CS), a sulfate-containing O-glycan naturally occurring in livestock and poultry products, and monitored the dynamic changes of microbial flores, inflammatory signatures, and pathogenic hallmarks. Results A metagenomic gut microbiota analysis revealed the overgrowth of sulfatase-secreting bacteria and sulfate-reducing bacteria in the gastrointestinal tracts of mice upon daily CS feeding. Sulfatase-secreting bacteria compromise gut integrity through prompting mucin degradation and mucus lesions, which were evident from the upregulation of secretary leukocyte protease inhibitor (SLPI) and mucin 1/4 (MUC-1/4). A synchronous elevation of lipopolysaccharide (LPS) and tumor necrosis factor α (TNF-α) levels in the serum as well as cerebral, hepatic, cardiac and muscular tissues suggests bacterial endotoxinemia, chronic low-grade inflammation and mitochondrial dysfunction, eventually leading to the onset of global inflammatory pathogenesis towards arthritis, dementia, tumor, and fatty liver. Conclusions CS triggers the early-phase and multi-systemic pathogenesis like arthritis, dementia, tumor, and fatty liver by enhancing gut opportunistic infection and evoking low-grade inflammation in mice. A plausible reason for the inconsistency of CS in treatment of osteoarthritis (OA) was also discussed.


Abstract Physical properties such as porosity and intact dry density (IDD) are compared with strength testing in relation to the Chalk formations in the cliffs of the English Channel. Natural moisture contents are close to saturation moisture contents for chalks with intact dry densities above 1.70 Mg/m3. Below this IDD, the natural moisture contents show a much greater range and greater divergence from the saturation line. There is also an indication that certain types of chalk retain water at saturation level while others gain and lose water more readily. Strength tests (Point Load Index, Brazilian Crushing Strength and Uniaxial Compressive Strengths) show up to four times reductions in strength between dry (higher strength) and saturated (lower strength) samples. Absence of a strong correlation between density and strength is interpreted as resulting from either mineralogical differences in the samples and/or textural differences between different chalks. The variation in physical properties and strength in the different chalks forming the cliffs indicates the strong stratigraphical and sedimentological controls on mechanical performance of the material and mass in cliff failures.


In Peer-to-Peer (P2P) networks it is not uncom- mon to find users that have initiated a file transfer and decide to leave the system before the end of the download. This is a particularly harmful behavior due to the resources (bandwidth or energy) wasted in such an aborted process. This negative effect is amplified when the systems conditions are such that the peers are not downloading at the maximum capacity. This is because in these conditions, there are not enough peers uploading the file, and a part of the bandwidth is wasted on peers that do not share their resources to the network once they leave the system. In this paper, the case of managed P2P networks is of special interest. As such, the variability in the transfer rates, such as the download and upload rates, is expected to be much less than in the case of the unmanaged P2P network. The limit case, where these transfer rates are constant is considered as an alternative to the exponential distribution. Additionally, two priority schemes are presented for a BitTorrent-based P2P network where the peers that are more likely to remain longer in the system are served first.


In contrast to sparse keypoints, a handful of line segments can concisely encode the high-level scene layout, as they often delineate the main structural elements. In addition to offering strong geometric cues, they are also omnipresent in urban landscapes and indoor scenes. Despite their apparent advantages, current line-based reconstruction methods are far behind their point-based counterparts. In this paper we aim to close the gap by introducing LIMAP, a library for 3D line mapping that robustly and efficiently creates 3D line maps from multi-view imagery. This is achieved through revisiting the degeneracy problem of line triangulation, carefully crafted scoring and track building, and exploiting structural priors such as line coincidence, parallelism, and orthogonality. Our code integrates seamlessly with existing point-based Structure-from-Motion methods and can leverage their 3D points to further improve the line reconstruction. Furthermore, as a byproduct, the method is able to recover 3D association graphs between lines and points / vanishing points (VPs). In thorough experiments, we show that LIMAP significantly outperforms existing approaches for 3D line mapping. Our robust 3D line maps also open up new research directions. We show two example applications: visual localization and bundle adjustment, where integrating lines alongside points yields the best results. Code is available at https://github.com/cvg/limap.


Multi-task benchmarks such as GLUE and SuperGLUE have driven great progress of pretraining and transfer learning in Natural Language Processing (NLP). These benchmarks mostly focus on a range of Natural Language Understanding (NLU) tasks, without considering the Natural Language Generation (NLG) models. In this paper, we present the General Language Generation Evaluation (GLGE), a new multi-task benchmark for evaluating the generalization capabilities of NLG models across eight language generation tasks. For each task, we continue to design three subtasks in terms of task difficulty (GLGE-Easy, GLGE-Medium, and GLGE-Hard). This introduces 24 subtasks to comprehensively compare model performance. To encourage research on pretraining and transfer learning on NLG models, we make GLGE publicly available and build a leaderboard with strong baselines including MASS, BART, and ProphetNet\footnote{The source code and dataset will be publicly available at this https URL.


Summary Deep vein thrombosis (DVT) is a common disease with an annual incidence of about 1 in 1000. Many risk factors have already been studied, both genetic and acquired. It is unclear whether obesity affects thrombotic risk in unselected patients. Obesity is common, with a prevalence of 20-25% and may therefore have a considerable impact on the overall incidence of thrombosis. We evaluated the risk of thrombosis due to overweight and obesity using data from a large population based case-control study. Four hundred and fifty-four consecutive patients with a first episode of objectively diagnosed thrombosis from three Anticoagulation Clinics in the Netherlands were enrolled in a case-control study. Controls were matched on age and sex to patients and were introduced by the patients. All patients completed a standard questionnaire and interview, with weight and height measured under standard conditions. The associations of obesity with clotting factor levels were studied to investigate possible mechanisms. Obesity (BMI ≥30 kg/m2) increased the risk of thrombosis twofold (CI95: 1.5 to 3.4), adjusted for age and sex. Obese individuals had higher levels of factor VIII and factor IX, but not of fibrinogen. The effect on risk of obesity was not changed after adjustment for coagulation factors levels (fibrinogen, F VIII, F IX, D-dimer). The relative risk estimates were similar in different age groups and in both sexes, indicating a larger absolute effect in older age groups. Evaluation of the combined effect of obesity and oral contraceptive pills among women aged 15-45 revealed that oral contraceptives further increased the effect of obesity on the risk of thrombosis, leading to 10-fold increased risk amongst women with a BMI greater than 25 kg/m2 who used oral contraceptives. Obesity is a risk factor for deep vein thrombosis. Among women with a BMI greater than 25 kg/m2 the synergistic effect with oral contraceptives should be considered when prescribing these.


Even though Article 81 and 82 EC apply to private undertakings and not to State regulations, the European Court of Justice established in Van Eycke that State regulations can come under antitrust scrutiny. This will happen in particular when the State delegates decision-making powers to private actors, enabling them to adopt decisions affecting the economic sphere. The Court has developed coherent case-law to describe what delegation means but its test fails to address the main concern: whether regulatory acts resulting from such delegation in reality emanate from the State or whether State approval merely shields private anti-competitive behaviour. Thus the borderline between State acts and private measures remains unresolved. In a delegation situation there is a risk that market actors will act in pursuance of their own interests and restrict competition, whilst at the same time obtaining immunity for their behaviour on the basis that it constitutes ``State action''. In the recent Mauri case the Court seems to be groping towards a stricter standard which requires that Member States ensure active supervision over ``delegated'' decisions rather than merely approve them formally. Additionally, in CIF the Court articulated a strict interpretation of the effet utile principle placing a large responsibility on Member States to ensure the full effectiveness of EC law in the field of competition. It is still unclear whether these changes result in a considerably tighter delegation test but Member States and their competition authorities---especially after the CIF judgment---will face a higher threshold when drawing the line between private and State measures. This article has been shortlisted for the 1st World Competition Young Writer Award.


Purpose – This paper aims to identify how leading companies are improving their strategy‐development processes to keep up with the transformations in the global competitive environment. The value of any reliable strategic foresight executives can wring from their planning systems can be priceless.Design/methodology/approach – BCG recently studied the strategy‐development processes of leading companies by interviewing more than 100 executives in 20 firms.Findings – The study found that leading firms are "stretching" their strategy process – along three mutually reinforcing dimensions: stretching time horizons, stretching their thinking, and stretching the engagement processPractical implications – Numerous examples of innovative best practices are given, for example: turn issues upside down. Instead of asking how to grow the business, ask how to kill it. Instead of feuding over how to increase resources (a typical budgetary debate), ask how to operate with significantly fewer resources, or even without the...


Since its entry on the European market, Uber has faced significant regulatory challenges, including lawsuits in several Member States. While some have described the opinions adopted by AG Szpunar in the Spanish and French preliminary ruling cases as a further setback for Uber, this paper shows that even if the CJEU was to follow the approach of AG Szpunar whereby Uber's activities are transport services rather than information society services as argued by the company and by certain intervening parties in the proceedings, its judgments would have little impact on Uber's activities. In fact, there is a regulatory momentum for Uber and other intermediation platforms as several Member States have adopted reforms aimed to regulate the services provided by these platforms in a way that allows them to operate at scale and contribute to improve urban mobility, while ensuring that these services are provided in a safe and transparent manner. This paper discussed these reforms and whether they meet good principles of regulation.


Succession of fish parasite fauna in lakes (with example of Baltic shield) was investigated. At the middle oligotrophic stage, the fauna of parasites and fishes maintain a relative stability for a long period and characterised by maximum species diversity.


Arsenic, mercury and cadmium compounds are used widespreadly in industry, agriculture and pharmaceutical manufacture. They are also listed as the important toxic substances to be controlled with top priorities by the U.S.A. Environmental Protection Agency. The specific aim of this study is to estimate the usage and amount of arsenic, mercury, and cadmium compounds in Taiwan area. Based on the analysis of official data and field survey, all materials of arsenic, mercury, and cadmium compounds were imported. The imported arsenic compounds were 574 kilotons in 1982, 769 kilotons in 1987 and 398 kilotons in 1990 (from January through August). These compounds were used mainly in pesticide and glass manufacturing industry. The imported mercury compounds were 10 kilotons in 1982, 48 kilotons in 1987 and 20 kilotons in 1990 (from January through August). They were used mainly in manufacturing Chinese pharmaceuticals and electronic utilities. The imported cadmium compounds were 174 kilotons in 1982, 477 kilotons in 1986. The imported amount of cadmium oxide was no longer reported after 1990. They were used in chemical manufacturing industry. In order to control the usage and amount of these toxic compounds effectively, it is important to enforce the official imported materials reporting system and a manufacture recording system of these compounds.


AIM
The purposes of this study are: (1) to evaluate symptomatology and psychological well-being, according to Ryff's theoretical model, of two groups of drug dependent patients in residential structures compared with a control; (2) to explore the impact of dual diagnosis, pharmacological therapy, duration of stay in structures and previous therapeutic experience as indicators on symptomatology and psychological well-being.

METHODS
The sample is formed by 61 drug-dependent patients and 65 controls. Each subject completed two self-administered scales: Kellner's Symptom Questionnaire-SQ and Ryff's Psychological Well-Being Scales-PWB. Differences in PWB and SQ mean scores between clinical and control subjects and within clinical group, for each specific variable, were analyzed using analysis of variance.

RESULTS
Clinical group had significantly lower levels of all six PWB dimensions and SQ scores compared to the controls. Dual diagnosis did not produce any significant effect on PWB and SQ general scores, except for the PWB dimension of positive social relations. Pharmacological therapy had a slightly significant effect only on PWB. No significant effects were found in terms of symptomatology and general well-being depending on duration of stay, except for purpose in life. Previous experience caused a significant result for psychological well-being, while no general effect on symptomatology was found.

DISCUSSION
We found that drug dependence is associated with high degree of symptomatology and the lack of positive psychological functioning in specific areas. Improving positive psychological functioning of this population could be a good way to intervene on specific problems which could interfere with treatment continuity.


Low mitochondrial number and activity have been suggested as underlying factors in obesity, type 2 diabetes, and metabolic syndrome. However, the stage at which mitochondrial dysfunction manifests in adipose tissue after the onset of obesity remains unknown. Here we examined subcutaneous adipose tissue (SAT) samples from healthy monozygotic twin pairs, 22.8–36.2 years of age, who were discordant (ΔBMI >3 kg/m2, mean length of discordance 6.3 ± 0.3 years, n = 26) and concordant (ΔBMI <3 kg/m2, n = 14) for body weight, and assessed their detailed mitochondrial metabolic characteristics: mitochondrial-related transcriptomes with dysregulated pathways, mitochondrial DNA (mtDNA) amount, mtDNA-encoded transcripts, and mitochondrial oxidative phosphorylation (OXPHOS) protein levels. We report global expressional downregulation of mitochondrial oxidative pathways with concomitant downregulation of mtDNA amount, mtDNA-dependent translation system, and protein levels of the OXPHOS machinery in the obese compared with the lean co-twins. Pathway analysis indicated downshifting of fatty acid oxidation, ketone body production and breakdown, and the tricarboxylic acid cycle, which inversely correlated with adiposity, insulin resistance, and inflammatory cytokines. Our results suggest that mitochondrial biogenesis, oxidative metabolic pathways, and OXPHOS proteins in SAT are downregulated in acquired obesity, and are associated with metabolic disturbances already at the preclinical stage.


Breast disease in the adolescent female is fortunately uncommon, with most presenting lesions being benign. The type and frequency of breast problems in young women less than 20 years of age are discussed in this paper. There were 634 adolescent females (9–19 years) referred to the Wesley Breast Clinic between January 1990 and December 1999. Of these, 62.6% were aged 18–19 years. The commonest reason for referral was a lump or thickening in the breast (n=554, 87.4%). Six hundred and nineteen females had ultrasound performed, with 59% showing no abnormality. The commonest abnormality in the remainder was probable fibroadenoma (n=162). Twenty-two percent of the females in the study had fine needle aspiration performed; none showed suspicious cytology. Twentythree females had an excision biopsy following their initial visit. Three of these were found to have benign phyllodes tumour. There were no malignancies detected, although one female had previous DCIS diagnosed elsewhere. # 2001 Harcourt Publishers Ltd


Excavated bamboo or wooden manuscripts dating from the 5th to 3rd centuries BCE have now become important new sources of data for Old Chinese phonology. The ways these sources are interpreted are necessarily based on methodological assumptions for Old Chinese reconstruction. So when debated issues in the latter are involved, disparate observations about the same materials turn out to manifest differences in the methodologies themselves. The study of Old Chinese through excavated manuscripts seems to become further complicated by considerations of the nature of the 'pre-Qin' archaic script and the provenances of the manuscripts. In response to these problems, as argued in this article, it is essential to recognize that the writings from the ancient Chu and Qin regions, notwithstanding the impressive range of graphic variability reaffirm the logographic nature of the Chinese writing system. The imperial 'script-unification' of the Qin dynasty was primarily an orthographic standardization in accordance with the norms of the old Qin region, whereby distinct regional variants were purged and preexisting internal variants were diminished. This by no means implicated such a drastic change in the writing system as a syllabary transforming to a logography. It is therefore necessary that the principles of OC reconstruction should be applied consistently to both the excavated archaic-script writings and transmitted early Chinese textual sources. It should be maintained first of all that the xiesheng (shared-phonophorics) and Shijing (the Book of Odes) rhymes in principle converge on a single phonological system, even though the actual history of the former is most probably older than the latter. This leads us to suppose about the OC vowel system that the Rounded Vowel Hypothesis does not hold, and that excavated texts have not yielded any data suggesting otherwise. Instead, this article suggests an alternative analysis of Middle Chinese (MC) -w- < *-w- which can explain the problem in the conventional OC rhyme classification concerning the Hypothesis. In the same vein, Chu and Qin writings in each case exhibit the early Chinese xiesheng series which had been received until that time; the regional variants thereof can complement each other as evidence for the Old Chinese phonology. When elements of dialects are found sporadically in the late archaic script, whether in Chu or Qin manuscripts, one may reasonably suspect that they reflect dialect-borrowings layered within the Old Chinese language.


To assess the direct cerebrovascular effects of clonidine, we investigated the pharmacological responses of pial vessels to its topical and IV administration using a cranial window.Forty-six dogs anesthetized with pentobarbital had the cranial window implanted. We administered six different concentrations of clonidine (10-8, 10-7, 10-6, 10-5, 10-4, 10-3 mol/L) dissolved in artificial cerebrospinal fluid under the window and measured the pial arterial and venous diameters. After pretreating pial vessels with either yohimbine, an alpha2-adrenoceptor antagonist, or glibenclamide, an adenosine triphosphate-sensitive K+-channel blocker, their action was examined after applying clonidine. We also evaluated the effects of IV clonidine (5 [micro sign]g/kg) on pial vascular tone. Topical clonidine produced significant constriction of the pial large and small arteries and veins in a concentration-dependent manner (P < 0.05). Yohimbine abolished the clonidine-induced pial arterial (large P < 0.005; small P < 0.0005) and venous constriction (large and small P < 0.0001). Glibenclamide potentiated the clonidine-induced pial arterial constriction (P < 0.05). IV clonidine did not cause significant changes in pial arteries, but it caused significant constriction of small veins. These were associated with a significant decrease in heart rate and an increase in serum potassium level and glucose concentration. In the present study, we demonstrate that the topical application of clonidine constricts both pial arterial and venous vessels in a concentration-dependent manner and suggest that mechanisms of such action are caused by the activation of alpha2-adrenoceptors and adenosine triphosphate-sensitive K+-channels, whereas IV clonidine constricts only pial small veins. Implications: In this study, we describe the direct and IV effects of clonidine on pial vessels using a cranial window in anesthetized dogs. The topical application of clonidine constricts pial vessels. This is mediated by the activation of alpha2-adrenoceptors and adenosine triphosphate-sensitive K+-channels. IV clonidine constricts only pial small veins.
(Anesth Analg 1998;86:766-72)


Since the discovery of high temperature superconductors (HTS) two decades ago, many anomalous properties have been reported. One of the most interesting properties is the possible existence of the stripe state consisting of one dimensional charge-density modulation coupled with some kind of spin ordering. X-ray and neutron scattering experiments and recently high resolution scanning tunneling microscopy have reported direct evidences of such a structure. In particular it has found in the La-Sr-Cu-O (LSCO) family the existence of the half-doped stripe with average of half a hole in one charge modulation period below and about 1/8 hole density. These results have fueled the idea about the presence of these charge or spin density wave states competing with the superconducting phase in underdoped HTS. They may even contribute to the pairing mechanism. In this talk, we will demonstrate that the presence of these stripes is actually a natural consequence of the strongly interacting t-J model by using a variational approach which provides a good enough accuracy to address the subtle result. Furthermore we show that half-doped stripes could be stabilized in hole-doped systems if we assume a simple electron-phonon interaction to renormalize the electron mass. However we have not found any evidence to support half-doped stripes in electron-doped systems.


The Rohingya crisis cast a long shadow over Myanmar in 2018, and prospects for the Rohingya refugees in Bangladesh were bleak. The peace process with ethnic armed organizations remained stalled. Myanmar signed major investment agreements with China that could have a dramatic effect on the economy.


Liberalization is generally credited with efficiency gains and growing economic performance. However, in the network industries such a vision is generally too simplistic, as economic performance is only one of the performance criteria – there is also technical and social performance (e.g., safety) – and as there probably economic performance tradeoffs between the different actors of the broad system (e.g., air transport system). Furthermore, the liberalization of the network industries is generally accompanied by an institutional process of re-regulation, whereby institutional arrangements are created so as to guarantee and balance the various performance objectives and actors' interests. So far, it has been difficult to evaluate the effects of a given regulatory institutional system on the performance of a liberalized industry as a whole. This paper will take the case of a national air transport system (including airlines, airports, and air traffic control), namely the case of Switzerland. It will first identify the main relevant and systemic economic, technical, and social performance criteria in the air transport industry. It will then describe the current institutional regulatory framework for the case of Switzerland. Finally, it will establish, for the case of Switzerland, a relationship between this institutional regulatory framework and the industry's performance. This paper, a case study of exploratory nature, is grounded in an already existing theoretical framework which links institutions to network industry performance. In its conclusion, it will try to generalize, from the case study of Switzerland, to other countries and institutional levels (e.g., EU), as it will also try to develop, from this case, a more dynamic conceptual model of how regulatory institutions relate to performance in the air transport system.


Objective Eplerenone (EPL) is a mineralo-corticoid receptor antagonist that is highly selective and has few side effects. This study was conducted to examine whether or not EPL treatment was able to reverse glomerular hyperfiltration, as an indicator of aldosterone renal action, in primary aldosteronism (PA) patients. Methods Changes in the estimated glomerular filtration rate (ΔGFR) were examined in 102 PA patients with EPL treatment. Furthermore, the sequential ΔGFR in 40 patients initially treated with EPL followed by adrenalectomy was examined in order to evaluate the extent of the remaining glomerular hyperfiltration in the patients treated with EPL. Results EPL decreased the GFR at 1 month after treatment. The GFR at baseline was the sole significant predictor for the ΔGFR. Patients initially treated by EPL followed by adrenalectomy showed three different ΔGFR patterns during the treatment, despite having comparable doses of EPL and comparable control of blood pressure and serum potassium levels. The urinary aldosterone excretion was significantly different among these three groups, and the group with no decrease in the GFR after EPL treatment showed greater urinary aldosterone excretion. Glomerular hyperfiltration was completely restored only in 17.5% of our unilateral PA patients after EPL treatment. Conclusion The present study revealed that blockade of aldosterone action by EPL could, at least partially, reverse glomerular hyperfiltration in PA. Whether or not these differential effects on the GFR affect the long-term outcome needs to be investigated, especially in patients with unilateral PA who do not want adrenalectomy and choose the EPL treatment option.


Traditionally, high-forage, low-concentrate diets fed ad libitum have been the primary system of feeding dairy heifers. However, high-concentrate diets can be fed at restricted intakes to reach desired rates of gain and increase nutrient efficiency. A total mixed ration containing high corn silage (CS; HCS: 77% CS, 23% concentrate) or low CS (LCS: 67% concentrate, 33% CS) was fed at restricted intakes in 2 trials to evaluate nutrient utilization by growing heifers. In the first trial, 4 ruminally cannulated heifers (298 +/- 16 kg of body weight) were fed to study differences in rumen pH, volatile fatty acid and ammonia concentrations, and mass of rumen contents. In situ determinations were made on the total mixed ration and CS. Low CS rations were digested more rapidly in situ when compared with HCS (4.5 vs. 2.3 +/- 0.3%/h), and no differences were observed in CS digestibility when incubated in the rumen of heifers fed either ration. Mean rumen pH tended to be lower for LCS than for HCS (5.9 vs. 6.2 +/- 0.1). Individual and total rumen volatile fatty acid concentrations and rumen ammonia concentration were not different between treatments. Total mass of rumen contents was lower for LCS. In the second trial, four 6-mo-old heifers (172 +/- 14 kg of body weight) and four 12-mo-old heifers (337 +/- 10 kg of body weight) were used. Digestibility of dry matter was greater for the LCS than the HCS diet in both age groups (76.3 vs. 71.1% for 12-mo-old heifers; 71.4 vs. 68.9% for 6-mo-old heifers). Apparent digestibility of N was not different between treatments; however, retained N was higher for the LCS diets for both age groups. Fecal output was significantly reduced in the LCS diets for both age groups. Feeding low-forage, high-concentrate diets to growing dairy heifers at restricted intakes, although more highly digestible, resulted in few significant differences in rumen fermentation patterns and lower fecal output.


INTRODUCTION
Oral premalignant lesions are conditions having high potential tendency for transformation into malignancy. The use of a conservative and effective treatment modality is one of the best strategies for cancer prevention. Photodynamic therapy (PDT) is a non-invasive method for topical and selective treatment of oral precancerous lesions. The present study was taken up to determine the efficacy of PDT in oral precancerous lesions.

METHODS
The study consisted 13 patients with 24 oral leukoplakia (OL) lesions and 8 with 20 oral lichen planus (OLP) lesions, divided into control and study groups. These lesions were affecting various intraoral sites, the buccal mucosa being the most common site followed by tongue and gingiva. The treatment regimen of PDT included 98% 5-aminolevulinic acid (5-ALA) which is topical applied and irradiated with light emitting diode (LED) of 420 nm wavelengths at several sessions.

RESULTS
In OL 16.6% of cases showed complete response, 66.6% partial response and 16.6% no response of the lesions to the treatment. In OLP 80% and 20% of the lesions showed partial and no response respectively. The differences with control groups for OL + OLP were found to be significant (P < 0.001).

CONCLUSION
Based on the results of the present study, we can conclude that PDT appears to be a feasible alternative to conventional therapy for oral premalignant lesions.


New Zealand Obese (NZO)/HlLt male mice exhibit a polygenic obesity and approximately 50% develop type 2 diabetes. This strain is known to produce a variety of autoantibodies, including autoantibodies to the insulin receptor. Because of their relatedness to the autoimmune-predisposed New Zealand Black (NZB) and New Zealand White (NZW) inbred strains, we compared NZO to its two related strains for shared hematologic and immunologic characteristics. Comparison of the three strains by serotyping and genotyping methods indicated that NZO shared with NZW the rare (recombinant) H2z haplotype at the major histocompatibility complex. Similar to the NZB and NZW strains, spleens from NZO mice contained increased numbers of CD19+CD43+ IgM+ B-1 B cells, a phenotype associated with natural autoantibody production. NZO mice developed a progressive microcytic anemia that was distinguished from NZB hemolytic anemia by absence of demonstrable antierythrocyte antibodies in the former. Outcross of NZO females with NZB males accelerated development of obesity and diabetes in F1 males. NZO males made B-lymphocyte–deficient by a disrupted immunoglobulin heavy chain gene did not become diabetic. These results suggest that NZO mice should be useful to investigators interested in studying the genetic contributions to autoimmunity made by the related NZW and NZB strains. Further, these results, combined with the pancreatic histopathology contained in the companion manuscript, suggest that B lymphocytes may be important contributors to diabetes pathogenesis in the NZO mouse.


Although balancing work and family commitments is a significant source of strain for working parents, working mothers in traditionally male positions face additional anxiety due to unfounded assumptions about their competence as employees, assumptions rooted in gender stereotypes. However, stereotype-based assumptions can also bias competence impressions of these working mothers in family domains, depicting them as bad parents. In four experimental studies, we documented evidence that working mothers are seen as less effective parents than nonworking mothers. Consistent with the argument that gender stereotypes underlie these findings, the bad parent assumption was apparent only for mothers and not fathers (Study 1), only when working in a male sex-typed occupation (Study 2), more intensely when job success was clear (Study 3), and only when working out of personal choice (Study 4). Similar patterns were observed in ratings of interpersonal appeal (e.g., likability, friend desirability, coworker desirability), relational judgments suggesting that there are also negative social consequences for working mothers.


In order to retrieve land surface component temperature from multi-spectral remote sensing images, such as ASTER, we choose a component equivalent emissivity model, and iterative linear regression inversion algorithm. The method is tested with ASTER image of VNIR and TIR channels, as well as supplementary and validation data acquired from ground experiment. The atmospheric effect is corrected with the dark-object method; surface structural information is derived from ASTER VNIR observations; component emissivity is measured in situ with the BOMEN MR-154 spectrometer; validation data are also measured in ground experiments. Finally, the accuracy of the results and sources of error are analyzed.


BACKGROUND
Aortic pulse wave velocity (PWV) is an indirect index of arterial stiffness and an independent cardiovascular risk factor. Consistency of PWV assessment over time is thus an essential feature for its clinical application. However, studies providing a comparative estimate of the reproducibility of PWV across different noninvasive devices are lacking, especially in the elderly and in individuals at high cardiovascular risk.

METHODS
Aimed at filling this gap, short-term repeatability of PWV, estimated with 6 different devices (Complior Analyse, PulsePen-ETT, PulsePen-ET, SphygmoCor Px/Vx, BPLab, and Mobil-O-Graph), was evaluated in 102 high cardiovascular risk patients hospitalized for suspected coronary artery disease (72 males, 65 ± 13 years). PWV was measured in a single session twice, at 15-minute interval, and its reproducibility was assessed though coefficient of variation (CV), coefficient of repeatability, and intraclass correlation coefficient.

RESULTS
The CV of PWV, measured with any of these devices, was <10%. Repeatability was higher with cuff-based methods (BPLab: CV = 5.5% and Mobil-O-Graph: CV = 3.4%) than with devices measuring carotid-femoral PWV (Complior: CV = 8.2%; PulsePen-TT: CV = 8.0%; PulsePen-ETT: CV = 5.8%; and SphygmoCor: CV = 9.5%). In the latter group, PWV repeatability was lower in subjects with higher carotid-femoral PWV. The differences in PWV between repeated measurements, except for the Mobil-O-Graph, did not depend on short-term variations of mean blood pressure or heart rate.

CONCLUSIONS
Our study shows that the short-term repeatability of PWV measures is good but not homogenous across different devices and at different PWV values. These findings, obtained in patients at high cardiovascular risk, may be relevant when evaluating the prognostic importance of PWV.


In order to investigate stress distribution of side plates on the logging truck's cable reel, and find the cause of side plates cracking, an elastic-plastic finite element model of three-dimension is set up. Based on a series of computations, the distributions of displacement and equivalent stress under the working conditions are analyzed, as well as the influence of the number of side plate floors on stress distribution. The results indicate the maximum equivalent stress is on the outside connection between side plate and cable reel, and the floors take the most part loads from steel cables. When the number of floors is greater than 11, increasing the floor number will not decrease the maximum equivalent stress obviously. The conclusion provides useful method and foundation for resolving floor cracking on logging trucks.


We report two cases of acute cervical angina and ECG changes induced by anteflexion of the head. Cervical angina is defined as chest pain that resembles true cardiac angina but originates from cervical discopathy with nerve root compression. In these patients, Prinzmetal's angina, valvular heart disease, congenital heart disease, left ventricular aneurysm, and cardiomyopathy were excluded. After all, the patient's chest pain was reproduced by anteflexion of head, at this time, their ECGs showed nonspecific ST-T changes in the inferior and anterior leads different from the basal ECG. ECG changes returned to normal when the patient's neck moved to the neutral position. To our knowledge, these are the first cases of cervical angina associated with acute ECG changes by neck motion.


The expression of the Bacillus subtilis W23 tar genes specifying the biosynthesis of the major wall teichoic acid, the poly(ribitol phosphate), was studied under phosphate limitation using lacZ reporter fusions. Three different regulation patterns can be deduced from these beta-galactosidase activity data: (i) tarD and tarL gene expression is downregulated under phosphate starvation; (ii) tarA and, to a minor extent, tarB expression after an initial decrease unexpectedly increases; and (iii) tarO is not influenced by phosphate concentration. To dissect the tarA regulatory pattern, its two promoters were analysed under phosphate limitation: The P(tarA)-ext promoter is repressed under phosphate starvation by the PhoPR two-component system, whereas, under the same conditions, the P(tarA)-int promoter is upregulated by the action of an extracytoplasmic function (ECF) sigma factor, sigma(M). In contrast to strain 168, sigma(M) is activated in strain W23 in phosphate-depleted conditions, a phenomenon indirectly dependent on PhoPR, the two-component regulatory system responsible for the adaptation to phosphate starvation. These results provide further evidence for the role of sigma(M) in cell-wall stress response, and suggest that impairment of cell-wall structure is the signal activating this ECF sigma factor.


The prototypical second-generation antipsychotic clozapine has been associated with various hematologic and metabolic adverse effects. Less attention has been given to clozapine's adverse cardiac effects, including myocarditis and cardiomyopathy, despite a high associated mortality rate. Here we present the case of a young man with psychosis who developed near-fatal myocarditis after the initiation of clozapine. We review the diagnosis, management, and hypothesized pathophysiology of clozapine-induced myocarditis. We urge clinicians to be vigilant for the condition and to balance the risk of myocarditis and other side effects against the many benefits of clozapine for patients with treatment-resistant symptoms of schizophrenia.


The purpose of this contribution is to highlight the role that European citizenship has come to play as a constraint on domestic administrative decisions on nationality. This dynamic can be illustrated by discussing the Rottmann decision, adopted by the European Court of Justice in March 2010[1].
The Rottmann judgement has been criticized essentially on the ground that it fails both to protect the right of the individual concerned not to be stripped off of his nationality and to acknowledge the autonomy of European citizenship vis-a-vis domestic nationality. In this paper, I argue that most of these criticisms are based on an error of perspective. Those who attack Rottmann seem to look at the case from a constitutional, if not philosophical, point of view, while the relevance of Rottmann should rather be assessed in an administrative law perspective.
Rottmann halts the idea of a European post-national citizenship, in so far as its acquisition and loss will still depend on the acquisition and loss of domestic nationality: Rottmann makes clear that, unless an amendment of the treaties takes place, no EU citizenship will emerge beyond the nation-state. My alternative claim is that European citizenship seems prone to become a post-nationalist (rather than post-national) legal tool, in so far as it pushes nationality beyond nationalism. After Rottmann, EU citizenship not only keeps limiting the power of the state to discriminate according to nationality, as it did before, but it also begins to constrain the discretion of domestic authorities in adjudicating nationality cases. That discretion, being built upon sovereignty and public order concerns, has been traditionally very wide. Behind it, nationalist instincts leading to ethnic or religious discriminations may still be easily hidden. Constraining administrative discretion in nationality cases in the name of European citizenship may serve the purpose of piercing the veil and make those discriminations less likely.
This argument will be developed in three stages. First, a brief illustration of the Rottmann case is provided. Secondly, some of the harshest criticisms addressed to that judgement are illustrated. Thirdly, a different reading of Rottmann is offered, which requires administrative lenses to be worn.


Sir, Subsequent to the report of a patient with ocular-oro genital ligneous disease by Rubin ei al. (1989) a letter was published by Buck & Ridley (1990) on her response to treatment with topical corticosteroids for the cervix. The patient was undergoing investigations for subfertility and at laparoscopy adhesions were found surrounding the fimbrial ends of the fallopian tubes. At the time of salpingolysis the tissue forming the adhesions was sent for histological examination. This revealed connective tissue with deposits of fibrinous material similar to that seen in previous biopsies of the cervix, i.e. consistent with ligneous disease. This phenomenon has not to our knowledge previously been reported in the literature. We shall have no further information on this patient since, unfortunately, she has been killed in a motor accident. C. M. Ridley H. Morgan Deparimenis of Dermatology and Gynaecology Whiitington Hospital Highgate Hill London N19 SNF


SUMMARY The gills are the major site of acid–base regulation in most fish. Acid–base transfer across fish gills is dominated by carbon dioxide and ammonia excretion, especially the former. Bicarbonate buffering in the blood is less than that found in mammals; regulation of ventilation has little effect on CO2 levels in the blood and control of ventilation is not used to regulate body pH in fish. Proton ATPase (freshwater fish), Na+/H+ exchangers (marine fish) and anion exchangers (marine and freshwater fish) are located in the gills. These transporters contribute to the regulation of internal pH, but little is known about how this is done in fish. Fish kept in confined water volumes acidify their environment, largely due to CO2. This acidification augments ammonia excretion and reduces ammonia toxicity. The possible involvement of ammonia recycling in acid excretion is also discussed.


Aluminosilicate and silicate porous solids have been evaluated as supports for triethylenediamine (TEDA) for the adsorption and decomposition of cyanogen chloride. A series of silica-gel supports has been used to study the effect of varying pore size. A series of faujasitic zeolites has been used to examine the effect of the cation exchange capacity of the support and the type of exchangeable cation. Results show that the activity of adsorbed TEDA towards cyanogen chloride appears to increase with increasing support pore diameter, and TEDA seems to be activated by basic adsorption sites on the support. Cesium-exchanged zeolite supports are particularly active. In general, zeolite supports appear to confer significantly higher activity to TEDA than traditional activated carbon supports. A series of mesoporous MCM-41 and AlMCM-41 supports has also been studied, but the activities of adsorbed TEDA are lower than expected. Significantly, the specific surface area of the inorganic supports does not seem to be a primary factor in controlling adsorbed TEDA activity.


Convolutional Neural Networks (CNNs) are widely used to solve classification tasks in computer vision. However, they can be tricked into misclassifying specially crafted `adversarial' samples -- and samples built to trick one model often work alarmingly well against other models trained on the same task. In this paper we introduce Sitatapatra, a system designed to block the transfer of adversarial samples. It diversifies neural networks using a key, as in cryptography, and provides a mechanism for detecting attacks. What's more, when adversarial samples are detected they can typically be traced back to the individual device that was used to develop them. The run-time overheads are minimal permitting the use of Sitatapatra on constrained systems.


Far-infrared optical and dielectric properties of ferroelectric SrTiO3 and BaTiO3 nanofibers, prepared by hydrothermal syntheses, were studied using terahertz time-domain spectroscopy. The power absorption, refractive index, and complex dielectric function were characterized in the frequency range from 0.2 to 1.0 THz. The measured results are well reproduced by theoretical fittings based on the dielectric models and the effective medium model. The study reveals that the low-frequency dielectric properties of the ferroelectric SrTiO3 nanofibers are associated with the lowest transverse optical (TO) soft mode TO1 at 2.70 THz (90.0 cm(-1)), and that of the ferroelectric BaTiO3 nanofibers are related to the lowest pair of transverse optical (TO) and longitudinal optical (LO) modes near 5.35 THz, which are both consistent with their bulk single-crystal and thin-film counterparts.


An area around railway station where was developed a long time ago In Seoul, requires overall maintenance, which is executed via several urban planning systems, such as a restoration of deteriorating buildings, a road maintenance, and a securing of public urban space. As well as an urban maintenance is increasingly being undertaken road maintenance and improvements by private sector recently. Thus, the private sector plays an important role in urban renewal and maintenance in urban areas. However, with exception of an urban planning district, road maintenance and improvement projects face several challenges; thus, an overall management plan needs to be implemented, as well as the system of compensation for road maintenance undertaken by the private sector. This paper aims to identify these challenges and discuss the role of city administration in road maintenance, as well as to offer suggestions about the part that the private sector can play in the maintenance of public urban facilities. This study consists of data collection through a literature review, interviews with city administration staff, and a case study of Hanrim Tower in Gwangjin-Gu, Seoul. In conclusion, we suggest how urban maintenance can be managed according to proposals from citizens regarding road maintenance and improvements, and recommend that city administration to set up definite criteria to incentivize enterprises that are willing to carry out the work. A maintenance of public urban facilities by private sector is particularly focused on road maintenance and improvements, which suggests the need for overall improvements to the urban planning system and the system of incentives.


Web lectures are a form of educational content that differs from classic hypertext in a number of ways. Web lectures are easier to produce and therefore large amounts of material become accumulated in a short time. The recordings are significantly less structured than traditional web based learning content and they are time based media. Both the lack of structure and their time based nature pose difficulties for navigation in web lectures. The approach presented in this paper applies the basic concept of social navigation to facilitate navigation in web lectures. Social navigation support has been successfully employed for hypertext and picture augmented hypertext in the education domain. This paper describes how social navigation can be implemented for web lectures and how it can be used to augment existent navigation features.


Seventeen CDDO-amino acid-NO donor trihybrids (4a-q) were designed and synthesized. Biological evaluation indicated that the most active compound 4c produced high levels of NO and inhibited the proliferation of drug-sensitive (HCT-8, IC50 = 0.294 μM) and drug-resistant (HCT-8/5-FU, IC50 = 0.232 μM) colon cancer cells, which were attenuated by an NO scavenger or typical substrate of PepT1. Furthermore, 4c triggered HCT-8 and HCT-8/5-FU cell apoptosis more strongly than CDDO-Me, inhibited the HIF-1α, Stat3, AKT, and ERK signaling, and induced the nitration of P-gp, MRP1, and BCRP proteins in HCT-8/5-FU cells. Finally, 4c had 4.36-5.53-fold less inhibitory activity against nontumor colon epithelial-like cells (CCD841, IC50 = 1.282 μM) in vitro and inhibited the growth of implanted human drug-resistant colon cancers in mice more potently than CDDO-Me. Together, 4c is a novel trihybrid with potent antitumor activity and may be a promising candidate for the treatment of drug-resistant colon cancer.


Genome-wide association (GWA) studies, which search for association between single, common genetic markers and a disease phenotype, have shown varying degrees of success. Recent studies suggest that multiple rare variants at different loci may act in concert to influence etiology of common diseases. However, current GWA studies depend upon the Common Disease Common Variant hypothesis and are not powered to account for disease-causing rare variants (CDRV). We consider a simple CDRV model where a subset of rare variants at a locus is independently deleterious. These rare variants have modest penetrance (their presence increases disease likelihood significantly), but each explains only a small fraction of the diseased individuals. For this model, we describe an algorithm that efficiently computes a subset of rare-variants that best associate with the disease. We test our approach using extensive simulations. Neutral rare-variants are simulated using coalescent models, and causal variants are simulated under selection using Wright's equation. Our method is robust in detecting associations with modest odds ratios in relatively small cohort studies. It significantly outperforms previously proposed strategies, and is robust to other CDRV models. Our simulations suggest that associated regions with an odds ratio of 1.2 can be identified with a cohort study of 10000 individuals. Those with an odds ratio of 1.5 can be identified with a cohort study of 5000 individuals. Regions with stronger association (odds ratio > 2:2) can be identified with cohort studies of 1500 individuals or less. The method was applied to a cohort of 289 individuals, 143 with high BMI and 146 with relatively low BMI. Two genes (187 kb) were sequenced in this cohort using next-generation sequencing. We identied two subsets of co-located variants that showed significant association with BMI (out of a total of 1088 rare variants). These subsets associated showed association with un-adjusted chi-square P-values of 3.6 x 10⁻⁴ and 1.4 x 10⁻⁴, and permutation based P-values of 0.004 and 8.04 x 10⁻⁴, respectively. In comparison, the most significant association using single marker tests had a chi-square P-value of 0.002. Our results suggest that whole genome association using an analysis of rare variants is feasible.


BACKGROUND: The pupillary dilation reflex (PDR), the change in pupil size after a nociceptive stimulus, has been used to assess antinociception during anesthesia. The aim of this study was to compare the antinociceptive properties of sevoflurane and desflurane by measuring the PDR amplitude. METHODS: Seventy patients between 20 and 55 years of age were randomly allocated to receive either sevoflurane or desflurane. The PDR amplitude after an electrical standardized noxious stimulation (SNT) was measured using an infrared pupillometer under 1.0 minimum alveolar concentration (MAC). The pupil diameter was measured from 5 seconds before to 5 minutes after the SNT. The mean arterial pressure (MAP), heart rate (HR), and bispectral index (BIS) were also measured immediately before and after SNT as well as 1 minute and 5 minutes after SNT. The primary outcome was the maximum percent increase from the prestimulation value of the pupil diameter, and the secondary outcomes were the maximum percent increase from the prestimulation value of the MAP, HR, and BIS after SNT. RESULTS: The maximum percent increase of the pupil diameter after SNT was not different between the 2 groups (median [first quartile to third quartile], 45.1 [29.3–80.3] vs 43.4 [27.0–103.1]; median difference, −0.3 [95% confidence interval, −16.0 to 16.5]; P = .986). Before SNT, the MAP was higher under 1.0 MAC of sevoflurane than desflurane; however, the maximum percent increase of MAP, HR, and BIS was not different between the 2 groups. CONCLUSIONS: The amount of change in the PDR amplitude, MAP, and HR after SNT was not different between sevoflurane and desflurane anesthesia. This result might suggest that sevoflurane and desflurane may not have different antinociceptive properties at equivalent MAC.


Background & objectives: Post-partum depression affects the mother's health, family relationships and child's training, negatively. Therefore, determining the related reasons, in especial in the women who have the first delivery and will experience the physical and mental changes of such event in their life is very important. Therefore, the aim of this study was to assess the role of social support as well as the kind of child delivery in order to predict the post-partum depression in such group of women. Methods: The statistical population of this correlational-descriptive study consists of all women in the nulliparous women who have been referred to the medical centers of Kerman during 2016. Among them, 205 were chosen by a cluster and convenience sampling methods. The measurement tools were including demographic features questionnaire, Edinburgh postnatal depression scale (EPDS), and social support questionnaire (MOS-SSS). Data were analyzed with SPSS software using logistic regression and T-test method. Results: In total, 102 individuals have degrees of postpartum depression and the rest of the patients were non-depressed.The results showed that the possibility of depression emergence in these women, after child delivery based on the decrease of factors such as emotional informational support, emotional support and positive social interaction support were about 40.18, 10.1 and 5.55%, respectively. Also, the possibility of depression in this group after delivery regarding the kind of delivery was 27%. As well, the women who had caesarian delivery significantly were more depressed rather than whom had natural delivery (p<0. 001). Conclusion: Based on the results of this study, more attention should be paid to increase social support for women who will go into the first labor; and also the preventive treatments must be considered for women give birth a child by caesarian section.


Monoclonal antibodies are widely used as diagnostic reagents and for therapeutic purposes, and their demand is increasing extensively. To produce these proteins in sufficient quantities for commercial use, it is necessary to raise the output by scaling up the production processes. This review describes recent trends in high-density cell culture systems established for monoclonal antibody production that are excellent methods to scale up from the lab-scale cell culture. Among the reactors, hollow fiber bioreactors contribute to a major part of high-density cell culture as they can provide a tremendous amount of surface area in a small volume for cell growth. As an alternative to hollow fiber reactors, a novel disposable bioreactor has been developed, which consists of a polymer-based supermacroporous material, cryogel, as a matrix for cell growth. Packed bed systems and disposable wave bioreactors have also been introduced for high cell density culture. These developments in high-density cell culture systems have led to the monoclonal antibody production in an economically favourable manner and made monoclonal antibodies one of the dominant therapeutic and diagnostic proteins in biopharmaceutical industry.


Visual dialog is a vision-language task where an agent needs to answer a series of questions grounded in an image based on the understanding of the dialog history and the image. The occurrences of coreference relations in the dialog makes it a more challenging task than visual question-answering. Most previous works have focused on learning better multi-modal representations or on exploring different ways of fusing visual and language features, while the coreferences in the dialog are mainly ignored. In this paper, based on linguistic knowledge and discourse features of human dialog we propose two soft constraints that can improve the model's ability of resolving coreferences in dialog in an unsupervised way. Experimental results on the VisDial v1.0 dataset shows that our model, which integrates two novel and linguistically inspired soft constraints in a deep transformer neural architecture, obtains new state-of-the-art performance in terms of recall at 1 and other evaluation metrics compared to current existing models and this without pretraining on other vision language datasets. Our qualitative results also demonstrate the effectiveness of the method that we propose.


The coupling of big Ge-arrays like EUROBALL or GASP with ancillary detectors for the study of the structure properties of very exotic nuclei, far from the stability valley, has given outstanding results in the last years. A large fraction of the experiments performed with both arrays has been devoted to study both proton-rich and neutron-rich nuclei populated using stable beams provided by the LNL Legnaro and MeS Strasbourg accelerators. Nuclei lying close to the N = Z line are of particular interest being a laboratory where collective excitations as well as fundamental properties of the nuclear force can be tested, like isospin symmetry and isospin breaking terms, proton neutron pairing, dripline effects and coherent neutron and proton contributions to the nuclear excitations. Some of this properties are more evident (degree of isospin mixing) or can be only observed (collective effects) in heavy N = Z nuclei. In this contribution we present the experimental results obtained by our collaboration along and in the vicinity of N = Z line.


Wildland firefighters are often called on to make tactical decisions under stressful conditions in order to suppress a fire. These decisions can be hindered by human factors such as insufficient knowledge of surroundings and conditions, lack of experience, overextension of resources or loss of situational awareness. One potential tool for assisting fire managers in situations where human factors can hinder decision-making is the Wildland-Urban Interface Evacuation (WUIVAC) model, which models fire minimum travel times to create geographic trigger buffers for evacuation recommendations. Utilising multiple combinations of escape routes and fire environment inputs based on the 2007 Zaca fire in California, USA, we created trigger buffers for firefighter evacuations on foot, by engine and by heavy mechanised equipment (i.e. bulldozer). Our primary objective was to examine trigger buffer sensitivity to evacuation mode and expected weather and fuel conditions. Evacuation travel time was the most important factor for determining the size and extent of modelled trigger buffers. For the examined scenarios, we show that WUIVAC can provide analytically driven, physically based triggers that can assist in entrapment avoidance and ultimately contribute to firefighter safety.


ABSTRACT Diverse organisms time their cellular activities to occur at distinct phases of Earth's solar day, not through the direct regulation of these processes by light and darkness but rather through the use of an internal biological (circadian) clock that is synchronized with the external cycle. Input pathways serve as mechanisms to transduce external cues to a circadian oscillator to maintain synchrony between this internal oscillation and the environment. The circadian input pathway in the cyanobacterium Synechococcus elongatus PCC 7942 requires the kinase CikA. A cikA null mutant exhibits a short circadian period, the inability to reset its clock in response to pulses of darkness, and a defect in cell division. Although CikA is copurified with the Kai proteins that constitute the circadian central oscillator, no direct interaction between CikA and either KaiA, KaiB, or KaiC has been demonstrated. Here, we identify four proteins that may help connect CikA with the oscillator. Phenotypic analyses of null and overexpression alleles demonstrate that these proteins are involved in at least one of the functions—circadian period regulation, phase resetting, and cell division—attributed to CikA. Predictions based on sequence similarity suggest that these proteins function through protein phosphorylation, iron-sulfur cluster biosynthesis, and redox regulation. Collectively, these results suggest a model for circadian input that incorporates proteins that link the circadian clock, metabolism, and cell division.


The potential for IL-5 to regulate human B cells is controversial despite its well established role as a regulatory factor for murine B cells. We hypothesized that the mechanism by which human B cells were stimulated would, as with murine B cells, determine their potential to respond to IL-5. Since Staphylococcus aureus Cowan strain I (SAC) and Moraxella catarrhalis (MCat) stimulate human B cells by distinct interactions with cell-surface Ig, we compared their potential to induce an IL-5-responsive state by human B cells purified to homogeneity. Neither SAC alone nor SAC plus IL-5 stimulated Ig production, although microgram quantities of IgM were produced with SAC plus IL-2. In contrast, MCat induced microgram quantities of IgM by B cells in the absence of exogenous cytokines, and IL-5 significantly increased IgM production over twofold in the majority of donors. Synergism of IL-5 and IL-2 was detected using suboptimal concentrations of IL-2 with MCat-, but not SAC-, stimulated B cells. Donor B cells unresponsive to IL-5 when stimulated with MCat, became IL-5 responsive in the presence of IL-2. Since message for the IL-5R alpha, IL-5R beta, and soluble IL-5R alpha chains was detected in freshly isolated B cells, we further investigated whether IL-5 responsiveness to MCat, but not SAC, was due to their differential regulation of IL-5R mRNA. Surprisingly, stimulation by either MCat or SAC, without or with IL-2, increased both IL-5R alpha and IL-5R beta mRNA and decreased soluble IL-5R alpha mRNA. These studies demonstrate that, as with murine B cells, human B cells express message for IL-5R but can respond to IL-5 only if appropriately stimulated to undergo terminal differentiation.


Like many writing center directors, I was hesitant to introduce online tutoring. However, because of limited physical space on campus, the internet provides the only room for growth available to us—a problem faced by many writing centers (Carpenter 2). The inevitability of online growth is also supported by the increase of tertiary-level online and blended courses being offered at most post-secondary schools. I was hesitant to begin online tutoring because [of] the "complexities introduced by online tutoring: the increased potential for directive tutoring instead of nondirective tutoring . . . the lack of sustained dialogue in asynchronous tutorials, and technological problems of accessibility and compatibility" (Kastman Breuch 21). In a conscious effort to avoid some of these issues, when the writing lab I direct began providing online tutorials in spring 2010. Our staff chose to use a software product called ShowDocument.com that allows students to upload their drafts and then share an interactive white board with the tutor to annotate the paper being discussed while synchronously chatting. The program does not have an audio or video function, so participants type their messages. We considered using a program such as Skype that would allow the tutor and student to see each other as they speak. However, technology is never completely trustworthy, and the ongoing issues of poor, broken, or failed transmission made Skype and similar programs an unreliable choice. Second, the close confines in which we work make the noise level in our lab high, and students themselves often login to video conferences from their dorms, or apartments, where background distractions can greatly impede the tutorial. Finally, as Lee-Ann Kastman Breuch suggests, we learned that we could not assume that all of our students who use the online service have access to equipment that enables them to use Skype or similar programs (21).


Abstract This work studied the effect of light-stressors, irradiance and photoperiod length on the status of hemolymph glutathione in two species of crayfish, Procambarus clarkii and Procambarus digueti. Adult animals of each species were submitted to two experimental approaches: (1) two batches of each species were placed under low or high light irradiant conditions of light–dark (LD) 24 h cycles of two different photoperiod lengths, one normal LD 12:12 and one extreme LD 20:4 low and high irradiance for 10 weeks. Time-dependent light changes on hemolymph glutathione concentration were determined throughout the entire experimental period; and (2) three batches of the two species were submitted to independent treatments consisting of the same LD 12:12 cycles of high and low irradiance and 20:4 high-irradiance LD cycles. Reduced and oxidized glutathione hemolymph concentrations were determined and total glutathione was calculated. In addition midgut glutathione reductase activity in both species was determined. The two species showed different hemolymph glutathione reactivity and glutathione status for the two light parameters. Dissimilar responses of both species, as well as the rate of mortality of P. digueti represent specific differences in the metabolic responses, as well as tolerance to photo-oxidative stress produced by light. The role of glutathione in the tolerance of crayfish to photo-oxidative stress is discussed.


ABSTRACT This article examines the narrated memory of a Swedish settler colony in northeast Argentina. Recently, scholarly attention has turned to how migrants of the nineteenth and early twentieth centuries contributed to colonizing processes in the Americas as they established themselves on lands already inhabited by Indigenous Peoples. The settlement of Swedish migrants in Misiones is here regarded as part of a strategy of settler colonialism advocated by the Argentine state in order to extend the agrarian frontier further and thereby 'civilise' and secure the nation's rural landscape through the presence of white settlers. From this perspective, the aim of the article is to understand how the historical macropolitical framework of settler colonialism in Argentina is interwoven in the collective and individual narratives of Swedish descendants in present-day Misiones. The article draws on ethnographic interviews and observations made in Misiones between 2017 and 2019. Semi-structured interviews were conducted with 34 individuals along with walk-along observations at seven Swedish community sites. The article argues that a central narrative of memory among the descendants of Swedish settlers relies upon certain elements crucial to settler colonial societies. However, while this narrative structure is intrinsic to settler colonialism, it must also be analysed as part of a migration narrative. This article brings forth new empirical material from a site in Latin America where Swedish migration history has not previously been studied ethnographically. Further, it brings the study of migration, colonial settlement, and indigenous dispossession together through its analysis of a settler narrative in the particular context of settler colonial history of Misiones.


Bond returns are known to exhibit mean reversion, autocorrelation, and other dynamic properties that differentiate them from stock returns. Index-linked bonds bring in further characteristics that complicate the task of modeling returns over time. Such models are essential, however, in strategic portfolio analysis and quantitative risk management. This article shows that the modeling of index-linked bond portfolios can be reduced to statistical modeling of the portfolio's yield to maturity and the underlying index. For these quantities, many well-established models already exist. Using historical data from 12 different markets, the authors show that the two risk factors consistently explain more than 98% of monthly return variations over the past decade, including the recent financial crisis.


As the concerns regarding global worming were increased, the pressure of greenhouse gas(GHG) emission reduction on mobile source was also increased. Carbon dioxides contribute over 90% of total GHG emission and the mobile source occupies about 20% of this CO2 emission. Therefore automotive exhaust is suspected to be one of the major reasons of the rapid increase in greenhouse effect gases in ambient air. In this study, in order to investigate CO2 emission characteristics from gasoline passenger cars(PC), which is the most dominant vehicle type in Korea, 106 vehicles were tested on the chassis dynamometer. CO2 emissions and fuel efficiency were measured. The emission characteristics by displacement, gross vehicle weight, vehicle speed and CVS-75/vehicle speed mode were discussed. Test modes were vehicle speed modes and CVS-75 mode that have been used to develop emission factors and to regulate for light-duty vehicle in Korea. It was found that CO2 emissions showed higher large displacement, heavy gross vehicle weight, low vehicle speed and CVS-75 mode than small displacement, light gross vehicle weight, high vehicle speed and vehicle speed mode, respectively. From these results, correlation between CO2 emission and fuel efficiency was also determined. The results of this study will contribute to domestic greenhouse gas emissions calculation and making the national policy for climate change.


Recently, webly supervised learning (WSL) has been studied to leverage numerous and accessible data from the Internet. Most existing methods focus on learning noise-robust models from web images while neglecting the performance drop caused by the differences between web domain and real-world domain. However, only by tackling the performance gap above can we fully exploit the practical value of web datasets. To this end, we propose a Few-shot guided Prototypical (FoPro) representation learning method, which only needs a few labeled examples from reality and can significantly improve the performance in the real-world domain. Specifically, we initialize each class center with few-shot real-world data as the ``realistic" prototype. Then, the intra-class distance between web instances and ``realistic" prototypes is narrowed by contrastive learning. Finally, we measure image-prototype distance with a learnable metric. Prototypes are polished by adjacent high-quality web images and involved in removing distant out-of-distribution samples. In experiments, FoPro is trained on web datasets with a few real-world examples guided and evaluated on real-world datasets. Our method achieves the state-of-the-art performance on three fine-grained datasets and two large-scale datasets. Compared with existing WSL methods under the same few-shot settings, FoPro still excels in real-world generalization. Code is available at https://github.com/yuleiqin/fopro.


The heart begins to beat before the brain is formed. Whether conventional hierarchical central commands sent by the brain to the heart alone explain all the interplay between these two organs should be reconsidered. Here, we demonstrate correlations between the signal complexity of brain and cardiac activity. Eighty-seven geriatric outpatients with healthy hearts and varied cognitive abilities each provided a 24-hour electrocardiography (ECG) and a 19-channel eye-closed routine electroencephalography (EEG). Multiscale entropy (MSE) analysis was applied to three epochs (resting-awake state, photic stimulation of fast frequencies (fast-PS), and photic stimulation of slow frequencies (slow-PS)) of EEG in the 1–58 Hz frequency range, and three RR interval (RRI) time series (awake-state, sleep and that concomitant with the EEG) for each subject. The low-to-high frequency power (LF/HF) ratio of RRI was calculated to represent sympatho-vagal balance. With statistics after Bonferroni corrections, we found that: (a) the summed MSE value on coarse scales of the awake RRI (scales 11–20, RRI-MSE-coarse) were inversely correlated with the summed MSE value on coarse scales of the resting-awake EEG (scales 6–20, EEG-MSE-coarse) at Fp2, C4, T6 and T4; (b) the awake RRI-MSE-coarse was inversely correlated with the fast-PS EEG-MSE-coarse at O1, O2 and C4; (c) the sleep RRI-MSE-coarse was inversely correlated with the slow-PS EEG-MSE-coarse at Fp2; (d) the RRI-MSE-coarse and LF/HF ratio of the awake RRI were correlated positively to each other; (e) the EEG-MSE-coarse at F8 was proportional to the cognitive test score; (f) the results conform to the cholinergic hypothesis which states that cognitive impairment causes reduction in vagal cardiac modulation; (g) fast-PS significantly lowered the EEG-MSE-coarse globally. Whether these heart-brain correlations could be fully explained by the central autonomic network is unknown and needs further exploration.