As the ultimate consumers, patients play an important role in the emergence, spread and control of bacterial resistance to antibiotics. Improved knowledge of antibiotics and the problem of resistance, as well as a better understanding of beliefs, pressures/concerns, and expectations, from both the patient's and physician's perspectives, are fundamental for controlling antibiotic use. There is growing evidence to suggest that empowering patients through implementation of patient-centered health-care strategies, such as shared decision-making, in conjunction with educational initiatives help to change attitudes and behavior, and improve access to and completion of appropriate antimicrobial therapy. This, in turn, may help to control the development and spread of resistance to antibiotics.


Objective: To establish Portuguese recommendations regarding the indications for ordering bone densitometry measurement to (DXA) and for starting treatment to prevent osteoporotic fractures.
 Methods: A multidisciplinary panel, representing a wide range of medical specialties and patient associations related to osteoporosis, as well as national experts in this field and in health economics, met to develop recommendations based on available evidence and expert consensus. Recently obtained data on the epidemiologic, economic and quality-of-life aspects of osteoporotic fractures in Portugal were used to support decisions.
 Results: Ten recommendations were developed covering the issues of indications for ordering DXA measurements and whom to treat with anti-fracture medications. Thresholds for assessment and intervention are based on the cost-effectiveness analysis of interventions at different thresholds of a ten-year probability of osteoporotic fractures, calculated with the Portuguese version of FRAX® (FRAX®Port), and taking into account Portuguese epidemiologic and economic data. Limitations of FRAX® are highlighted and guidance for appropriate adjustment is provided, when possible.
 Conclusions: Cost-effectiveness thresholds for DXA examination and drug intervention aiming at fragility fracture prevention are provided for the Portuguese population. These are practical, based on national epidemiological and economic data, evidence-based, and supported by a multidisciplinary panel of experts and scientific societies. Implementation of these recommendations has the possibility to assure the most effective use of health resources in the prevention of osteoporotic fractures in Portugal.


Molecular dynamics simulation of the penicillin- and penem-acylated enzymes reveals that the conformational flexibility of the acyl moieties in the binding cleft and the conformational change of the acyl moieties are crucial for deacylation. The water molecule adjacent to the Glu 166 residue is not the nucleophile for deacylation, but construction of a model of the oxyanion tetrahedral intermediate suggested a plausible role of the water molecule as a proton donor for the oxyanion to facilitate the deacylation.


The objective of this study was to evaluate in individuals applications at clinical high risk of mental disorder with Diffusion Tensor Imaging (DTI-MRI). This provides an important opportunity for pathological mechanisms of Schizophrenia Disease (SD) and Alzheimer Disease (AD), related to mental disorder. All disease is associated with abnormal activity distributed spatially in neural systems with mediate the motor and cognitive manifestations of this disorder in combination with processing and visualization techniques for Diffusion Tensor Magnetic Resonance Imaging (DTI-MRI). It is possible that metabolic MRI studies have demonstrated that this illness is characterized by a set of reproducible functional brain networks that correlate with these clinical features. The time at which these abnormalities appear is unknown, as is their relationship to concurrent clinical and indices of disease progression. We therefore need to set vivo biomarkers that can distinguish the differing pathologies and their contribution to the clinical features of the conditions. Diffusion tensor imaging (DTI) utilizes the anisotropic nature of diffusion in neuronal white matter tracts. With neuronal degeneration, the mean diffusivity (MD) increases with the loss of structural barriers that restrict normal diffusion, and diffusion becomes less directionally oriented, which is associated with a reduction in fractional anisotropy (FA). Areas of reduced FA in subjects with lateral ventricle were found primarily in occipital parietal area with white matter tracts; in AD, it was also associated with reduced FA in the points the left thalamus.


Effects of mental stress (a 20-min modified Stroop's color-word conflict test; CWT) on the absorption of 12Sl-labeled soluble human insulin (10 U s.c. in the thigh 60 min before CWT) and on subcutaneous adipose tissue blood flow (ATBF; 133Xe clearance); heart rate (HR); arterial blood pressure (BP); and arterial levels of epinephrine (Epi), norepinephrine (NE), and glycerol were studied in 11 healthy subjects. Insulin absorption was measured as elimination of radioactivity (external ycounting) and as appearance of plasma immunoreactive insulin (IRI). The glucose-clamp technique was used to maintain normoglycemia. Identical measurements were performed during a control day without CWT. HR and mean BP increased markedly (35 ± 5 beats/min and 30 ± 3 mmHg) during CWT despite only minor elevations in plasma catecholamines. Thus, arterial plasma Epi rose from 0.18 ± 0.03 to 0.82 ± 0.17 nM (P < .01) and NE from 0.94 ± 0.09 to 1.69 ± 0.18 nM (P < .001). ATBF showed a biphasic response, with a 100% elevation during CWT followed by a decrease and a second peak of similar magnitude ∼0.5 to 1 h after CWT. Blood glycerol was approximately doubled during CWT and remained elevated during recovery. Despite these changes, insulin absorption was unaltered during and after stress. Thus, elimination rates of 125I, plasma IRI levels, and amounts of glucose needed to maintain normoglycemia were all similar during the stress and control days. These results suggest that absorption of soluble insulin from subcutaneous injection sites in the thigh is unaltered during potent mental stress in healthy subjects despite a considerable and prolonged increase in ATBF.


Studies were performed on 5 patients with idiopathic dysotnia‐parkinsonism, each of whom had minor dystonic movements and parkinsonian symptoms with marked diurnal fluctuation. Levels of homovanillic acid and 5‐hydroxyindoleacetic acid were not defferent from those in controls. Considerable improvement in dystonic movements and parkinsonian symptoms was obtained with a small dose of L‐dopa, trihexyphenidyl hydrochloride, amantadine, or bromocriptine hydrochloride. Electrophysiological investigation confirmed that the dystonic movements, which became remarkably worsened on attempted movement, contributed importantly to the diurnal fluctuation of symptoms.


Scattered data interpolation by radial kernel functions leads to linear equation systems with large, fully populated, ill-conditioned interpolation matrices. A successful iterative solution of such a system requires an efficient matrix-vector multiplication as well as an efficient preconditioner. While multipole approaches provide a fast matrix-vector multiplication, they avoid the explicit setup of the system matrix which hinders the construction of preconditioners, such as approximate inverses or factorizations which typically require the explicit system matrix for their construction. In this paper, we propose an approach that allows both an efficient matrix-vector multiplication as well as an explicit matrix representation which can then be used to construct a preconditioner. In particular, the interpolation matrix will be represented in hierarchical matrix format, and several approaches for the blockwise low-rank approximation are proposed and compared, of both analytical nature (separable expansions)...


The paradigm of skew-tolerant parallel asynchronous communication was introduced by Blaum and Bruck (see ibid., vol. 39, 1993) along with constructions for codes that can tolerate or detect skew. Some of these constructions were improved by Khachatrian (1991). In this paper these constructions are improved upon further, and the authors prove that the new constructions are, in a certain sense, optimal. >


PURPOSE
To examine the expression of bFGF in the developing bovine retina.

METHODS
Fetal bovine eyes at 90, 120, 150, and 180 days gestational age, as well as adult bovine eyes, were immunohistochemically stained for the presence of bFGF. Detailed characterization of the anti-bFGF antibodies by immunoblot and Western blot analysis against pure FGF gene family standards and crude extracts of bovine retina were also performed.

RESULTS
Expression of bFGF occurs beginning at 150 days of gestation, a period when photoreceptor development and secondary capillary network development is in process. No bFGF expression was found at 90 days, but primary capillaries were already apparent at this stage of development.

CONCLUSIONS
Expression of bFGF in the developing bovine retina may play a functional role in outer retinal development.


Wearable technologies' popularity in sporting practices continues to grow. Runners use GPS watches and activity trackers to track steps, log miles, map courses, and monitor heart rates. Likewise, wearables are integrated into long distance running events, with race officials relying on technologies to effectively execute events. However, technologies can also enable and monitor cheating. Many studies focusing on the individual explore why cheaters make unethical decisions. Actor-Network Theory shifts cheating's focus from the individual and moral failings to an assemblage that includes not only the runner, but nonhumans, such as technology, as well. A 2015 Canadian Ironman cheating incident case study illuminates intricate relationships and networks between humans and nonhumans. By examining the intersections of cheating and technology in running sports, the authors see where and how technology works as intended or is repurposed. Whereas a human-centered approach to sport and cheating dismisses wearables' agency, Actor-Network Theory reveals their underexamined, sociotechnical complexities.


Wintertime surface ocean heat loss is the key process driving the formation of Subantarctic Mode Water (SAMW), but there are few direct observations of heat fluxes, particularly during winter. The Ocean Observatories Initiative (OOI) Southern Ocean mooring in the southeast Pacific Ocean and the Southern Ocean Flux Station (SOFS) in the southeast Indian Ocean provide the first concurrent, multiyear time series of air–sea fluxes in the Southern Ocean from two key SAMW formation regions. In this work we compare drivers of wintertime heat loss and SAMW formation by comparing air–sea fluxes and mixed layers at these two mooring locations. A gridded Argo product and the ERA5 reanalysis product provide temporal and spatial context for the mooring observations. Turbulent ocean heat loss is on average 1.5 times larger in the southeast Indian (SOFS) than in the southeast Pacific (OOI), with stronger extreme heat flux events in the southeast Indian leading to larger cumulative winter ocean heat loss. Turbulent heat loss events in the southeast Indian (SOFS) occur in two atmospheric regimes (cold air from the south or dry air circulating via the north), while heat loss events in the southeast Pacific (OOI) occur in a single atmospheric regime (cold air from the south). On interannual time scales, wintertime anomalies in net heat flux and mixed layer depth (MLD) are often correlated at the two sites, particularly when wintertime MLDs are anomalously deep. This relationship is part of a larger basin-scale zonal dipole in heat flux and MLD anomalies present in both the Indian and Pacific basins, associated with anomalous meridional atmospheric circulation.


This paper attempts to extract a fundamental trend, which we call a " trend-cycle component," from an economic time-series. The "trend-cycle component" consists of a medium-term business cycle component and a long- term trend component. The objective is to eliminate the short-term irregular and seasonal variations that hide a fundamental trend in an economic time-series. We test five different time-series methods. Among them, the Henderson moving average (which is incorporated in an X-12- ARIMA seasonal adjustment program), the Band-Pass filter (which utilizes a Fourier transformation), and the DECOMP are found to be effective in extracting a "trend-cycle component" with a cyclical period longer than 1 .5 years. However, no method is found to be effective in extracting a " long-term trend component" with a cyclical period longer than that of a medium-term business cycle. Although the HP filter is somewhat successful , it still contains a component with a cyclical period of about three years that corresponds to a business cycle. These methods are useful for forecasting a wide variety of economic variables because they reveal a fundamental trend in the time series. In addition, statistical programs are available for easy application. They have, however, a few shortcomings. First, it is often difficult to provide a meaningful economic interpretation of the revealed characteristics of the "trend- cycle component." Second, the addition of new data can change the estimation results. In particular, an extracted component around the end of a sample period is likely to be revised with new data. Special caution is in order, therefore, in interpreting the estimation results and forecasting the time series when the data exhibit large variations. In this case, comparing the results of different methods provides a useful way to assess the reliability of an extracted "trend-cycle component."


BACKGROUND
Focal segmental glomerulosclerosis (FSGS) is one of the most common patterns of glomerular injury encountered in human renal biopsies. Epithelial hyperplasia, which can be prominent in FSGS, has been attributed to dedifferentiation and proliferation of podocytes. Based on observations in a mouse model of FSGS, we pointed to the role of parietal epithelial cells (PECs). In the present study we investigated the relative role of PECs and podocytes in human idiopathic FSGS.

METHODS
We performed a detailed study of lesions from a patient with recurrent idiopathic FSGS by serial sectioning, marker analysis and three-dimensional reconstruction of glomeruli. We have studied the expression of markers for podocytes, PECs, mesangial cells, endothelium, and myofibroblasts. We also looked at proliferation and composition of the deposited extracellular matrix (ECM).

RESULTS
We found that proliferating epithelial cells in FSGS lesions are negative for podocyte and macrophage markers, but stain for PEC markers. The composition of the matrix deposited by these cells is identical to Bowman's capsule.

CONCLUSION
Our study demonstrates that PECs are crucially involved in the pathogenesis of FSGS lesions.


Tumor volume and changes in tumor characteristics over time are important biomarkers for cancer therapy. In this context, FDG-PET/CT scans are routinely used for staging and re-staging of cancer, as the radiolabeled fluorodeoxyglucose is taken up in regions of high metabolism. Unfortunately, these regions with high metabolism are not specific to tumors and can also represent physiological uptake by normal functioning organs, inflammation, or infection, making detailed and reliable tumor segmentation in these scans a demanding task. This gap in research is addressed by the AutoPET challenge, which provides a public data set with FDG-PET/CT scans from 900 patients to encourage further improvement in this field. Our contribution to this challenge is an ensemble of two state-of-the-art segmentation models, the nn-Unet and the Swin UNETR, augmented by a maximum intensity projection classifier that acts like a gating mechanism. If it predicts the existence of lesions, both segmentations are combined by a late fusion approach. Our solution achieves a Dice score of 72.12\% on patients diagnosed with lung cancer, melanoma, and lymphoma in our cross-validation. Code: https://github.com/heiligerl/autopet_submission


OBJECTIVE
IL-15 decreases lipid deposition in preadipocytes and decreases the mass of white adipose tissue in rats, indicating that IL-15 may take part in regulating this tissue. IL-15 is expressed in human skeletal muscle and skeletal muscle may be a source of plasma IL-15 and in this way regulate adipose tissue mass.

DESIGN
The relation between skeletal muscle IL-15 mRNA expression, plasma IL-15, and adipose tissue mass was studied in 199 humans divided into four groups on the basis of obesity and type 2 diabetes. Furthermore, using a DNA electrotransfer model, we assessed the effect of IL-15 overexpression in skeletal muscle of mice.

RESULTS
In humans, multiple regression analysis showed a negative association between plasma IL-15 and total fat mass (P<0.05), trunk fat mass (P<0.01), and percent fat mass (P<0.05), independent of type 2 diabetes. Negative associations were also found between muscle IL-15 mRNA and obesity parameters. IL-15 overexpression in skeletal muscle of mice reduced trunk fat mass but not sc fat mass.

CONCLUSIONS
Our results indicate that IL-15 may be a regulator of trunk fat mass.


Traditional pattern mining methods usually work on single data sources. However, in practice, there are often multiple and heterogeneous information sources. They collectively provide contextual information not available in any single source alone describing the same set of objects, and are useful for discovering hidden contextual patterns. One important challenge is to provide a general methodology to mine contextual patterns easily and efficiently. In this paper, we propose a general framework to encode contextual information from multiple sources into a coherent representation---Contextual Information Graph (CIG). The complexity of the encoding scheme is linear in both time and space. More importantly, CIG can be handled by any single-source pattern mining algorithms that accept taxonomies without any modification. We demonstrate by three applications of the contextual association rule, sequence and graph mining, that contextual patterns providing rich and insightful knowledge can be easily discovered by the proposed framework. It enables Contextual Pattern Mining (CPM) by reusing single-source methods, and is easy to deploy and use in real-world systems.


Subcutaneous interferon beta-1a (Rebif) therapy has been recognized as a significant advance in the treatment of relapsing-remitting multiple sclerosis (MS). The drug is supplied as a solution in a ready-to-use prefilled syringe. Given the chronic nature of the disease, a convenient and simple drug delivery for self-administration improves patient management. Home-based therapy requires comprehensive knowledge of multiple sclerosis and a training and support program to ensure maximum convenience and independence for the patient. These result in high compliance with therapy and optimum response to treatment.


Effects of 2-bromo-alpha-ergocryptine (CB 154) on plasma prolactin luteinizing hormone (LH) and testosterone levels accessory reproductive glands and spermatogenesis were studied in lambs during puberty. 18 lambs born during normal lambing season (February and 10 lambs born during the nonlambing period (October) and received a daily injection of CB 154 (2 gm) from the 10th week after birth until the 21st week. Treatment resulted in a highly significant (p less than .001) decrease in the concentration of plasma prolactin but did not affect LH or testosterone levels. There was no marked decrease in testis weight in the treated animals and the establishment of spermatogenesis was not delayed by the treatment. However there was a significant decrease in the weight of the seminal vesicles (p less than .01) and in their fructose concentration (p less than .01 and p less than .05). These results indicate that prolactin may play a role in the secretory activity of these glands in the male lamb.


The article deals with the internal deep structure of the earth's crust of the East European platform and the surface of the mantle lithosphere. The presented charts of the three main layers of the earth's crust — the lower, middle and upper and the surface of the mantle lithosphere — for the first time identified deformation by changing the thickness of the layers. Deformations are compared on all layers that allowed to allot the active center, the main (through) and local (developed in separate layers) areas. The boundaries of these regions are active zones of different ranks. The observed end-to-end development of strain from layer to layer or expression of some of them only in separate layers indicates on the sub-horizontal stratification and vertical divisibility of the earth's crust. Deformations of the deep layers are compared with the latest near-surface platform structures. This made it possible to establish a connection of near-surface deformations with deep ones and to consider the latter as the latest. These studies are relevant for solving fundamental problems of the origin of new structures and a number of practical problems.


Coupled thermal and hydrologic flow processes have been recognized as important factors in the evaluation of Yucca Mountain as a potential repository for high-level radioactive wastes. As a result, several models and numerical codes such as TOUGH2 have been used to investigate the thermohydrologic conditions near a potential nuclear waste repository. However, very few of these models have been tested through laboratory or field scale studies. This work has therefore focused on modeling well-controlled experiments of non-isothermal flow processes in porous media at different scales to serve two primary objectives: (1) identify processes that are potentially important to thermal and hydrologic transport at Yucca Mountain and (2) build confidence in models and codes through combined experimental and numerical studies of thermohydrologic behavior at different scales and conditions. In this report, three independent studies of thermohydrologic flow processes at laboratory and field scales are presented. The experiments and field studies that are presented here were performed independently of this work. The main focus of this report was to use the numerical code TOUGH2 to simulate the non-isothermal flow behavior observed in each experiment to generate understanding of the thermohydrologic processes and to gain confidence in the code. TOUGH2 was chosen duemore » to its current use in calculations associated with Yucca Mountain and its capability of modeling the coupled transport of air, water, vapor, and heat in porous media.« less


Introduction: Disaster, Trauma, and Respect for the Dead 1. At War with Nature: Coverage of Natural Disaster Fatalities 2. Death Rites Interrupted: Responsibility and Remembrance in Coverage of the Tri-State Crematory Scandal and Hurricane Katrina 3. Who Speaks for the Dead?: Authority and Authenticity in News Coverage of the Amish School Shootings - Lessons Learned from Life Stories 4. Life and Death in a Small Town: Cultural Values and Memory in Community Newspaper Obituaries 5. 'It Takes a Sinner to Appreciate the Blinding Glare of Grace': Redeeming the 'Dark' Celebrity 6. 'We Can't Keep Losing our Kids': Fear, Blame and Mourning in Press Coverage of Teen Deaths 7. Mourning 'Men Joined in Peril and Purpose': Working-Class Heroism in News Repair of the Sago Miners' Story - The Journalism of Ritual and Tribute 8. 'Portraits of Grief' and Stories that Heal: The Public Funeral for Victims of September 11 9. Reporting on 'a Grieving Army of Americans': Citizen Testimony in the Misremembering of Ronald Reagan 10. 'All the Fellows that Went on Before Me': Tribute, Memory and Counter-Memory among Veterans of 'the Good War' Conclusion


States increasingly rely on self-defence to justify forcible measures against terrorists. It seems agreed that when so doing, they must comply with the traditional conditions of necessity and proportionality. The application of these two principles to anti-terrorist self-defence raises a number of complex issues. drawing on a detailed examination of case studies, the present paper addresses these issues and suggests how necessity and proportionality can be applied meaningfully.


INTRODUCTION Despite effective endocrine treatments, endocrine resistance remains a major clinical challenge. We and other groups have recently detected ligand-binding domain ESR1 mutations in metastatic estrogen receptor positive ( ER+) breast cancers. Our preclinical studies showed that these mutations confer constitutive activity and relative resistance to tamoxifen and fulvestrant. In this study we sought to investigate therapeutic strategies to overcome resistance rendered by the ESR1 mutations. Since our previous studies showed relative resistance to tamoxifen or fulvestrant, we hypothesized that bazedoxifene, a high affinity third generation SERM/SERD could overcome resistance driven by the ER mutant resistance. Additionally, we hypothesized that inhibiting cyclin D1, a key ER transcriptional target gene and cell cycle regulator, is a second potential therapeutic strategy to circumvent resistance rendered by mutant ER. Therefore in this study we tested the effects of bazedoxifene, palbciclib and their combination on cell proliferation in the presence and absence of the ESR1 mutations. METHODS For this study we established doxycycline inducible MCF7 cell lines expressing the ER-LBD mutations (Y537S, Y537N and D538G) and WT-ER as control. Cell proliferation response to bazedoxifene, tamoxifen, fulvestrant, palbociclib and the bazedoxifene-palbociclib combination was evaluated. RESULTS Cells harboring mutant ER were relatively resistant to tamoxifen and fulvestrant, as expected, and remained sensitive to single agent bazedoxifene and palbociclib. The combination of bazedoxifene and palbociclib was found to be superior to the single agents and exhibits synergistic activity. CONCLUSION The combination of bazedoxifene and palbociclib inhibits mutant ER cell growth and other cell models of endocrine resistance and is a potential therapeutic combination. Citation Format: Nguyen M, Buchwalter G, Luo F, Garraway L, Brown M, Jeselsohn R. Exploring bazedoxifene and palbociclib as potential therapeutic strategies for overcoming ESR1-mediated endocrine resistance. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-05-09.


Abstract. Currents recorded at two stations positioned at the Adriatic shelf break between 17 February and 6 March 1989 were considered. They provided the first evidence of current variability related to the Adriatic-wide seiches. Current spectra were dominated by a peak at 21.1h – a well-known period of the fundamental Adriatic mode. Amplitudes of oscillations were considerable, occasionally greater than 30cm/s. Both along- and cross-basin currents were recorded, thus signalling the importance of rotational effects. Comparison of the current data with the sea-level measurements performed simultaneously along the east Adriatic coast showed that the 21-h currents flowing in the Adriatic preceded sea levels by a quarter of a cycle, as would be expected from a simple model of bay seiches. Sea-level amplitudes reached 40cm in the North Adriatic, thus marking the event as one of the strongest on record. Seiching was triggered by a suddenly changing sirocco wind, as is usually the case in the Adriatic. The most important features of the seiche event were reproduced with a two-dimensional hydrodynamic model of the Adriatic Sea, forced by the sea-level residuals measured at Otranto and the air pressure and wind data recorded at Lastovo. The model showed that the seiche-related currents were relatively strong in the area where the current measurements were performed and further north – between Zadar and Ancona. Key words. Oceanography: general (continental shelf processes) – Oceanography: physical (sea-level variations, currents)


For pt.1see ibid., vol. 9, p. 3 (2007). In this paper, the task and user interface modules of a multimodal dialogue system development platform are presented. The main goal of this work is to provide a simple, application-independent solution to the problem of multimodal dialogue design for information seeking applications. The proposed system architecture clearly separates the task and interface components of the system. A task manager is designed and implemented that consists of two main submodules: the electronic form module that handles the list of attributes that have to be instantiated by the user, and the agenda module that contains the sequence of user and system tasks. Both the electronic forms and the agenda can be dynamically updated by the user. Next a spoken dialogue module is designed that implements the speech interface for the task manager. The dialogue manager can handle complex error correction and clarification user input, building on the semantics and pragmatic modules presented in Part I of this paper. The spoken dialogue system is evaluated for a travel reservation task of the DARPA Communicator research program and shown to yield over 90% task completion and good performance for both objective and subjective evaluation metrics. Finally, a multimodal dialogue system which combines graphical and speech interfaces, is designed, implemented and evaluated. Minor modifications to the unimodal semantic and pragmatic modules were required to build the multimodal system. It is shown that the multimodal system significantly outperforms the unimodal speech-only system both in terms of efficiency (task success and time to completion) and user satisfaction for a travel reservation task


We provide a characterization of the peak age of information (AoI) achievable in a random-access system operating according to the frameless ALOHA protocol. Differently from previous studies, our analysis accounts for the fact that the number of terminals contending the channel may vary over time, as a function of the duration of the previous contention period. The exact characterization of the AoI provided in this paper, which is based on a Markovian analysis, reveals the impact of some key protocol parameters such as the maximum length of the contention period, on the average peak AoI. Specifically, we show that setting this parameter so as to maximize the throughput may result in an AoI degradation.


A search of the Streptomyces avermitilis genome reveals that its closest homologs are several O-methyltransferases. Among them, one gene (viz., saomt5) was cloned into the pET-15b expression vector by polymerase chain reaction using sequence-specific oligonucleotide primers. Biochemical characterization with the recombinant protein showed that SaOMT5 was S-adenosyl-L-methionine-dependent Omethyltransferase. Several compounds were tested as substrates of SaOMT5. As a result, SaOMT5 catalyzed Omethylation of flavonoids such as 6,7-dihydroxyflavone, 2',3'-dihydroxyflavone, 3',4'-dihydroxyflavone, quercetin, and 7,8-dihydroxyflavone, and phenolic compounds such as caffeic acid and caffeoyl Co-A. These reaction products were analyzed by TLC, HPLC, LC/MS, and NMR spectroscopy. In addition, SaOMT5 could convert phenolic compounds containing ortho-dihydroxy groups into Omethylated compounds, and 6,7-dihydroxyflavone was known to be the best substrate. SaOMT5 converted 6,7- dihydroxyflavone into 6-hydroxy-7-methoxyflavone and 7-hydroxy-6-methoxyflavone, and caffeic acid into ferulic acid and isoferulic acid, respectively. Moreover, SaOMT5 turned out to be a Mg2+-dependent OMT, and the effect of Mg2+ ion on its activity was five times greater than those of Ca2+, Fe2+, and Cu2+ ions, EDTA, and metal-free medium.


Dissimilatory nitrate reductase (Nar) was solubilized and partially purified from the large particle (mitochondrial) fraction of the denitrifying fungus Fusarium oxysporum and characterized. Many lines of evidence showed that the membrane-bound Nar is distinct from the soluble, assimilatory nitrate reductase. Further, the spectral and other properties of the fungal Nar were similar to those of dissimilatory Nars of Escherichia coli and denitrifying bacteria, which are comprised of a molybdoprotein, a cytochrome b, and an iron-sulfur protein. Formate-nitrate oxidoreductase activity was also detected in the mitochondrial fraction, which was shown to arise from the coupling of formate dehydrogenase (Fdh), Nar, and a ubiquinone/ubiquinol pool. This is the first report of the occurrence in a eukaryote of Fdh that is associated with the respiratory chain. The coupling with Fdh showed that the fungal Nar system is more similar to that involved in the nitrate respiration by Escherichia coli than that in the bacterial denitrifying system. Analyses of the mutant species of F. oxysporum that were defective in Nar and/or assimilatory nitrate reductase conclusively showed that Nar is essential for the fungal denitrification.


Two types of genes (Adk-a, and Adk-b) encoding for adenylate kinase (AK, EC 18.104.22.168.) were isolated from the cDNA library constructed from poly(A)+ RNA of rice (Oryza sativa L.). Two cDNAs were heterogeneous at 5' and 3' ends of non-coding sequences and had possible polyadenylation signals. One of the genes, Adk-a, had 1154 bp sequences encoding 241 amino acid residues, while the other type, Adk-b, contained 1085 bp sequences encoding for 243 amino acid residues. Homology between Adk-a and Adk-b was 73.7% in nucleotide sequences, and 90.8% in amino acid level. Two genes showed about 53% homology to bovine mitochondrial adenylate kinase (AK2) at nucleotide and amino acid levels. Concerning the codon usage of rice AK genes, T was abundant at the third position of a codon in the reading frames. In order to examine the enzyme activity of the protein encoded by the rice cDNA, Adk-a was cloned into an expression vector, pUC119, which was introduced into Escherichia coli strain CV2, a temperature-sensitive mutant of adenylate kinase. We found that the transformant carrying the rice Adk-a gene in the sense orientation recovered cell growth at non-permissive high temperature (42 degrees C) and expressed enzyme activities higher than the untransformed CV2 and the transformant possessing Adk-a cDNA in the antisense orientation. These observations suggest that rice Adk-a codes a biologically active enzyme. Furthermore, sucrose was found to regulate the transcription of AK genes in rice cell cultures. Organ related accumulation of mRNA in whole plants was also found.


Summary A padlock probe is a circularized oligonucleotide containing complementary sequences of target regions. Padlock probes combined with rolling-circle amplification enable fluorescence in situ hybridization (FISH) to reproducibly detect the genomic position of low or single-copy DNA sequences. The FISH with padlock probes revealed that a plant gene cluster of tandemly arrayed three paralogues responsible for photosynthesis rapidly moved from the interior subnuclear region to the peripheral subnuclear region in response to light. Using a pair of peptide nucleic acids as a double-strand opener for the target region, the efficiency of FISH with padlock probes at the detection of a single-copy genomic region was much improved. FISH with padlock probes will give us reliable data of dynamics, arrangement and position of a specific single locus in both the nucleus and the con-densed chromosomes.


In the past two decades the steady growth of seaborne trade has resulted in the
increase of container ships, container ports and their terminals. The structure of the
shipping market is, moreover, continuously evolving. On the carrier side, shipping
companies form consortia and alliances; on the port side, global terminal operators
and dedicated container terminals are emerging. The aim of this research is to
evaluate the efficiency of container ports and terminals and to study how to improve
the scale efficiency of any particular port/terminal. In particular we study how certain
factors influence the efficiency of container ports and terminals.
Regional container ports and global container terminals are examined based on the
econometrics benchmarking method Stochastic Frontier Analysis (SFA). Two datasets
are used, a panel dataset for 32 container ports in the North Mediterranean Sea over a
nine-year period, and a cross-sectional dataset for 165 container terminals worldwide.
Net-effect and gross-effect SFA models are applied to both datasets.
Technical, scale and overall efficiencies of individual ports/terminals are evaluated.
Operation and investment strategies are examined for selected ports and terminals.
The majority of the container ports and terminals in our North Mediterranean Sea
samples are found to be technically inefficient: 90% of container ports have their
technical efficiency lower than 0.80; 95% of container terminals have their technical
efficiency lower than 0.80. The research concludes that trading volume plays a key
role in the efficiency of a container port. The annual percentage increase in port
output is slower than what the technological improvement allows. Container terminals
are proven to be more productive than multiple purpose terminals. Global terminal
operators were not proven to out-perform local terminal operators as was expected. It was also found that the container terminal operation industry is over-scaled. The
research findings here can potentially affect decisions made by carriers, terminal
operators and policy makers, as it provides an overview of efficiencies for all
container ports/terminals in the two datasets and also examines in detail the sources of
inefficiency for individual ports.


The authors performed a number of experiments aiming at quantifying the infarct size in Sprague-Dawley male rats. The experimental model employed was isoproterenol (ISP) induced, infarctlike myocardial lesions. In quantifying the extent of the infarct area they compared the cross reliability of enzymatic and histological methods. ISP was administered in two subcutaneous injections (50 mg/100 Gm body weight) at a 24 hour interval. At the peak of the necrotic process (48 hrs after the first injection), the heart was subjected to enzymatic or histological studies. Thus, a group of infarcted animals (n = 25) and their controls (n = 15) underwent the assessment of creatine kinase (CK) content in the homogenate of the myocardium. Another group of animals (n = 15) was used for histological observations, including measurement of infarct size by planimetry from histological sections. A good relationship was observed between the percentage of necrotic tissue calculated on the basis of CK values (69.11 +/- 2.39%) and the infarction area assessed by planimetry (72.37 +/- 2.69%) (mean +/- standard error of the mean [SEM]). Thus, the present study confirms that ISP-induced myocardial lesions are a simple and reliable model for experimental infarct. Moreover, the assessment of the CK content in the heart is correlated with histological studies by planimetry, and is suggested as a direct enzymatic method to quantify the extent of myocardial necrosis.


Objectives:Many low andmiddle income country (LMIC) decision makers rely on data from multi-topic household surveys to identify the proportion of the population that has been reached with nutrition services, but these surveys do not always account for the quality of the services. Effective coverage cascades, commonly used in health systems research, capture measures of both coverage and quality to generate actionable information to improve nutrition programs, interventions, and policies. This study aims to describe the operationalization of effective coverage cascades for maternal and child nutrition interventions delivered through the health system using extant data in LMICs. Methods: By linking household survey and health facility assessment data from seven LMICs, effective coverage cascades were developed for nutrition interventions delivered through antenatal care visits and sick-child visits. Facility readiness and provision of care index scores were defined for each intervention from clinical guidelines and an expert survey, then refined based on data availability. The facility readiness and provision of care scores were linked to individual careseeking episodes from household survey data based on geographic domain and facility type. Finally, steps of the coverage cascade for each service in each country were estimated. Results:National estimates of the effective coverage cascade for each set of nutrition interventions will be presented. Analysis is ongoing, however preliminary findings show gaps in service readiness such as lack of provider training and gaps in provision of care such as limited nutrition counseling. A substantial drop is seen from service contact to input-adjusted coverage to quality-adjusted coverage for both antenatal care and sick child care. Conclusions:The cascade approach yielded summarymeasures that were useful for identifying high-level barriers to effective coverage; however, detailed measures within the cascade may be more useful for evidence-based decision making. Data availability on quality of care for nutrition interventions is scant, highlighting an opportunity to expand facility-based surveys to include nutrition interventions delivered through the health system. Funding Sources: Bill & Melinda Gates Foundation through the DataDENT initiative and the Improving Measurement and Program Design grant.


. In a revision of annual Silene species some interesting specimens were observed, which belonged to the species that had not been previously reported in detail from Iran. In this paper S. nocturna from the section Scorpioideae was added to the checklist of the third important genus of the flora of Iran, i.e. Silene , and new localities for S. gallica from the section Lasiocalycinae were reported. The description, geographical distribution in Iran and photos of each species were also presented.


Mycoplasma gallisepticum is the major mycoplasmal pathogen in poultry. The present study was undertaken to evaluate the efficacy of six commonly used antimicrobials, including difloxacin, enrofloxacin, ciprofloxacin, doxycycline, gentamicin, and valnemulin, against Mycoplasma gallisepticum, using a Monte Carlo simulation based on the pharmacokinetics-pharmacodynamic (PKPD) theory. The ratio of area under the free concentration vs. time curve for 24 h over MIC (AUC24h/ MIC) served as the PK-PD indices for fluoroquinolones, doxycycline and valnemulin, with the target levels at more than 70 h, 125 h, and 125 h, respectively. The maximum concentration of free drug over MIC (Cmax/MIC) served as the PK-PD index for gentamicin, with the target level at more than 12. In the analysis of drug sensitivity, the MIC50/90 values were as follows: difloxacin, 1/2 μg/mL; enrofloxacin, 0.5/2 μg/mL; ciprofloxacin, 1/2 μg/mL; doxycycline, 2/4 μg/mL; gentamicin, 2/4 μg/mL; and valnemulin, 0.008/0.03 μg/mL, respectively. The probabilities of achieving the PK-PD indices for difloxacin and enrofloxacin were lower (0-6.01%) than ciprofloxacin (27.34-36.67%) which was similar with gentamicin (31.65-45.82%). The lowest probability (0%) was obtained for doxycycline because of its high plasma protein binding, while the highest probability was obtained for valnemulin (90.34-97.95%). The results of this study showed that treatment with valnemulin may be the optimal choice for Mycoplasma gallisepticum infection.


Symphurus diabolicus, previously known only from the holotype collected in 501 m west of Isla San Cristobal (Chatham Island), Galápagos Archipelago, is re-described based on the holotype (112.6 mm SL) and 19 additional specimens (61.1-123.5 mm SL) recently collected from deep waters around the Galápagos Archipelago. Symphurus diabolicus is characterized by: an elongate body; narrow head with pointed snout; 1-3-2 ID pattern; 106-110 dorsal-fin rays; 89-96 anal-fin rays; 12 caudal-fin rays; 57-59 total vertebrae; 5 hypurals; extremely small scales; no pupillary operculum; large, prominent eyes, with migrated eye near dorsal margin of head; relatively short postorbital head length; relatively long snout and predorsal lengths; black peritoneum visible through abdominal wall on both sides of body; uniform olive green to dark brown ocular-side coloration with series of prominent, darker brown, elliptical to rectangular, blotches (not usually forming crossbands) along body at bases of dorsal and anal fins; and uniformly whitish or light yellow blind side. Symphurus diabolicus appears to be endemic to the Galápagos Archipelago, and is relatively common (captured at 16 different localities) at depths of 308 to 757 m (observed as shallow as 245 m) in this region. Examination of this expanded series of specimens confirms the validity of S. diabolicus and provides characters to distinguish it from S. microlepis Garman, a similar species known only from the holotype taken at approximately 530 m off Pacific Panama.


Neural network based approaches to automated story plot generation attempt to learn how to generate novel plots from a corpus of natural language plot summaries. Prior work has shown that a semantic abstraction of sentences called events improves neural plot generation and and allows one to decompose the problem into: (1) the generation of a sequence of events (event-to-event) and (2) the transformation of these events into natural language sentences (event-to-sentence). However, typical neural language generation approaches to event-to-sentence can ignore the event details and produce grammatically-correct but semantically-unrelated sentences. We present an ensemble-based model that generates natural language guided by events. Our method outperforms the baseline sequence-to-sequence model. Additionally, we provide results for a full end-to-end automated story generation system, demonstrating how our model works with existing systems designed for the event-to-event problem.


Accurate stroke lesion segmentation is a critical step in the neuroimaging processing pipeline to assess the relationship between post-stroke brain structure, function, and behavior. While many multimodal segmentation algorithms have been developed for acute stroke neuroimaging, few are effective with only a single T1-weighted (T1w) anatomical MRI. This is a critical gap because most stroke rehabilitation research relies on a single T1w MRI for defining the lesion. Although several attempts to automate the segmentation of chronic lesions on single-channel T1w MRI have been made, these approaches have not been systematically evaluated on a large dataset. Here, we performed an exhaustive review of the literature and identified one semi- and three fully automated approaches for segmentation of chronic stroke lesions using T1w MRI within the last ten years: Clusterize, Automated Lesion Identification, Gaussian naïve Bayes lesion detection, and LINDA. We evaluated each method on a large T1w stroke dataset (N=181) using visual and quantitative methods. LINDA was the most computationally expensive approach, but performed best across the three main evaluation metrics (median values: Dice Coefficient=0.50, Hausdorff's Distance=36.34 mm, and Average Symmetric Surface Distance = 4.97 mm), whereas the Gaussian Bayes method had the highest recall/least false negatives (median=0.80). Segmentation accuracy in all automated methods were influenced by size (small: worst) and stroke territory (brainstem, cerebellum: worst) of the lesion. To facilitate reproducible science, we have made our analysis files publicly available online at https://github.com/npnl/elsa. We hope these findings are informative to future development of T1w lesion segmentation algorithms.


Leptospirosis is a death-causing disease caused by corkscrew-shaped bacteria, Leptospira especially in
tropical countries. Current study was aimed to detect pathogenic, intermediate and saprophytic Leptospira species using polymerase chain reaction (PCR) assay from an oil palm plantation in Borneo, specifically in Miri, Malaysia. Materials and Methods: A total of 63 samples from rodents (n = 3), water (n = 30) and soil (n = 30) were isolated from an oil palm estate in Northern Sarawak, Borneo. All samples were inoculated into modified semisolid Ellinghausen-McCullough-Johnson-Harris (EMJH) broth with 5-fluorouracil and incubated for a month. Polymerase chain reaction (PCR) was performed using primer targeting lipL32 (423 bp) for pathogenic, 16S rRNA (331 bp) for intermediate and rrs (240 bp) for saprophytic species.

Results: pathogenic Leptospira was found in 33.3% rodents (1/3) Rattus tiomanicus, 23.3% soil samples (7/30) and 16.7% water samples (5/30). Intermediate species were demonstrated in the other 66.7% rodents (2/3), Sundamys muelleri and Rattus exulans and 10% soil samples (3/30). Saprophytic species was found in only 3.3% soil sample (1/30). Results from DNA sequencing analysis indicated that the most dominant pathogenic Leptospira species discovered in the study was Leptospira interrogans, followed by Leptospira noguchii and Leptospira weilii. Conclusion: These preliminary findings provide baseline data on the occurrence of Leptospira species in captured rodents and the environment. These findings could assist in control and prevention of leptospirosis among oil palm estate workers in Sarawak. Awareness and knowledge on leptospirosis should be promoted among oil palm workers for prevention and mitigation


Purine auxotrophy is a typical marker for many laboratory yeast strains. Supplementation of additional purine source (like adenine) is necessary to cultivate these strains. If not supplied in adequate amounts, purine starvation sets in. We tested purine starvation effects in budding yeast Saccharomyces cerevisiae ade8 knockout. We explored effects brought by purine starvation in cellular, central carbon metabolism and in the global transcriptome level. We observed that cells cultivated in purine depleted media became significantly more tolerant to severe thermal, oxidative and desiccation stresses when compared to the cells cultivated in media with all necessary supplements. When starved for purine, cells stop their cell cycle in G1 or G0 state; intracellular concentration of ATP, ADP and AMP decreases, but adenylate charge remains stable. Intracellular RNA concentration decreases and massive downregulation of ribosomal RNA occurs. We think that purine auxotrophic starvation in a way mimics "natural" nitrogen or carbon starvations and therefore initiates elements of a transcriptional program typical for stationary phase cells (cell cycle arrest, increased stress resistance). Therefore our results demonstrate that organised metabolic response is initiated not only via "natural starvations", but also when starving for metabolic intermediates, like purines.


We present an overlapping-generations model with two interacting teams, where young team members earn an income, whereas old team members depend on either intrateam transfers from young members (voluntary solidarity) or tax-financed transfers (compulsory solidarity). We derive the individually and team-specifically optimal decisions and present further behavioral hypotheses, including the crowding out of voluntary by compulsory solidarity. We test our hypotheses in an experimental study and examine (1) whether raising taxes crowds out voluntary transfers, (2) how income distributions influence voluntary and compulsory solidarity, and (3) whether participants prefer more to less compulsory solidarity.


Abstract Background: In Canada, contemporary collaborative professional learning models for educators utilise multiple forms of evidence to inform practice. Commonly, two forms of evidence are prioritised: (a) research-based evidence and (b) classroom-based evidence of student learning. In Ontario, the integration of these two forms of evidence within professional learning is increasingly facilitated by 'middle leaders' – school district level educators who support system change through sustained school- and classroom-embedded professional development with teachers. Purpose: This study investigated the role of the middle leader in supporting teachers' use of research- and classroom-based evidence within the context of collaborative professional learning. It was guided by the following research questions: (a) What is the capacity of middle leaders to use research- and classroom-based evidence within professional learning contexts? (b) What challenges do middle leaders encounter in using research- and classroom-based evidence within professional learning contexts? and (c) How do middle leaders develop their capacity for evidence use within professional learning contexts? Programme Description: The context for this study was a three-year networked professional learning project that included nine school districts in Ontario, Canada. An evidence-based collaborative inquiry approach was used to explore the common goal of improving mathematics teaching and learning across the nine districts. Participants: A purposeful sample of 30 middle leaders (i.e. system facilitators) and 54 teachers (36 Primary/Junior school teachers [student ages 4–11] and 18 Intermediate/Senior school teachers [student ages 12–18]) across the nine school districts was selected based on these educators' high degree of engagement in the project and willingness to participate in data collection. System facilitators were relative experts in mathematics instruction and provided differentiated and embedded support in mathematics pedagogy to school inquiry teams (i.e. school administrators and selected teachers), responsive to their local needs and goals. Design and Methods: A qualitative approach was used, comprising focus groups conducted at the end of each project year with study participants. Data collection yielded 27 system facilitator focus groups (nine per year) and 27 teacher focus groups (also nine per year), each transcribed verbatim. Findings: Standard thematic coding of focus group data was used to elucidate four emergent themes across system facilitators and teachers: (a) realising the need for data literacy in the construction of classroom evidence, (b) challenges to evidence use, (c) support enabling evidence use and (d) changing attitudes about evidence. Overall, findings indicated that both middle leaders and teachers required data literacy to use, successfully, classroom evidence within a collaborative inquiry. Although middle leaders encountered challenges to facilitating teachers' classroom evidence use in collaborative inquiry, they developed their own data literacy through regular cross-district middle leader learning sessions and targeted support from pedagogical and research experts. While both middle leaders and teachers shifted their attitudes and practices with respect to classroom evidence use within the project, this finding did not extend to their critical interrogation of research evidence sources (i.e. research literacy). Conclusions: Middle leaders play a central role in promoting evidence use within networked collaborative professional learning. Diverse strategies are needed to support middle leaders' use of both research- and classroom-based evidence throughout collaborative inquiry cycles, to inform and monitor classroom, school, district and regional impacts. While increased data literacy may enhance educators' use of classroom evidence, it may not directly impact their uptake of research to inform their collaborative inquiries.


The authors investigate the overall and subarea influence of a comprehensive set of marketing and marketing-related journals at three points in time during a 30-year period using a citation-based measure of structural influence. The results show that a few journals wield a disproportionate amount of influence in the marketing journal network as a whole and that influential journals tend to derive their influence from many different journals. Different journals are most influential in different subareas of marketing; general business and managerially oriented journals have lost influence, whereas more specialized marketing journals have gained in influence over time. The Journal of Marketing emerges as the most influential marketing journal in the final period (1996–97) and as the journal with the broadest span of influence across all subareas. Yet the Journal of Marketing is notably influential among applied marketing journals, which themselves are of lesser influence. The index of structural influence is significantly correlated with other objective and subjective measures of influence but least so with the impact factors reported in the Social Sciences Citation Index. Overall, the findings demonstrate the rapid maturation of the marketing discipline and the changing role of key journals in the process.


In the above-named work by Giannakis and Swami (see ibid., vol.38, no.3, p.478, 1990), an order selection procedure was proposed for parameter estimation for noncausal, nonminimum phase ARMA (autoregressive moving average) models of non-Gaussian processes. The commenter argues that it has been derived under an erroneous assumption, and he also gives a counterexample to show that it does not yield a consistent order estimate in general. Two linear approaches for parameter estimation were also presented in the above-named work. The commenter contends that an existing counterexample to an earlier version of one of the algorithms also applies to both the approaches of the above-named work. The authors' reply is presented. >


ABSTRACT In the last few years, BTK inhibitors, PI3K inhibitors, and venetoclax have been approved for clinical use against chronic lymphocytic leukemia (CLL), both as single agents, and in combination. This article summarizes recent achievements in the treatment of patients with CLL, and pays special attention to novel targeted drugs and monoclonal antibodies (Mabs). A literature search was conducted of the PubMed and Google Scholar databases. Rituximab and obinutuzumab have been combined with chemotherapy, and more recently, with BTK inhibitors, PI3K inhibitors, and venetoclax. These agents have demonstrated high activity in treatment naïve (TN) and relapsed or refractory (RR) CLL. Immunochemotherapy regimens are currently considered in TN younger patients with IGHV-mutated disease and should not be given in patients without IGHV mutation. BTK inhibitors are more commonly used as monotherapy in TN and RR patients. PI3K inhibitors can be combined with CD20 Mabs, but their use in CLL is limited due to safety concerns. Venetoclax is typically combined with anti-CD20 Mabs in CLL. Generally, the optimal sequencing of therapies remains to be established, and the selection of upfront therapy needs to be tailored to the individual patient.


This paper presents a novel position estimation scheme for interior permanent magnet synchronous machines (IPMSMs) based on merging two self-sensing techniques according to the operating speed. High frequency (HF) signal injection algorithm is deployed for zero and low- speeds, while a Machine Learning (ML) method is solicited for medium and high speeds. The scheme is intended for sensorless torque-controlled drives used in electric vehicle (EV) propulsion. Typically, the proposed sensorless strategy can be applied to safety and limphome applications.


Wind energy and wave energy are considered to have enormous potential as renewable energy sources in the energy system to make great contributions in transitioning from fossil fuel to renewable energy. However, the uncertain, erratic, and complicated scenarios, as well as the tremendous amount of information and corresponding parameters, associated with wind and wave energy harvesting are difficult to handle. In the field of big data handing and mining, artificial intelligence plays a critical and efficient role in energy system transition, harvesting and related applications. The derivative method of deep learning and its surrounding prolongation structures are expanding more maturely in many fields of applications in the last decade. Even though both wind and wave energy have the characteristics of instability, more and more applications have implemented using these two renewable energy sources with the support of deep learning methods. This paper systematically reviews and summarizes the different models, methods and applications where the deep learning method has been applied in wind and wave energy. The accuracy and effectiveness of different methods on a similar application were compared. This paper concludes that applications supported by deep learning have enormous potential in terms of energy optimization, harvesting, management, forecasting, behavior exploration and identification.


Perfluorohexanesulfonic acid (PFHxS) is one of the persistent organic pollutants that has been recommended to be listed in Annex A of the Stockholm Convention. It has gained increasing attention in recent years due to its toxic effects. The guideline values of PFHxS are commonly associated with PFOS in various countries and regulatory agencies. In this study, multispecies bioassays were conducted to determine the ecological toxic effects of PFHxS, including plants, soil invertebrates, and soil microorganisms, which indicated the EC10/NOEC values ranged from 2.9 to 250 mg/kg. Where possible, logistic models were used to calculate the EC30 values for various endpoints. The species sensitivity distributions were employed to estimate the ecological investigation levels for PFHxS contamination in soils using toxicity results from literature and this study. The calculation using EC10/NOEC values from both literature and this study indicated a most conservative HC5 as 1.0 mg/kg (hazardous concentration for 5 % of the species being impacted). However, utilisation of EC30 values derived from this study resulted in a much higher HC5 for PFHxS in contaminated soils (13.0 mg/kg) which is at the higher end of the existing guideline values for PFOS for protecting ecological systems. The results obtained in this study can be useful in risk assessment processes to minimize any uncertainty using combined values with PFOS.


Objective: To assess the effectiveness of a program of preventive physical therapy for the elderly using parameters linked to quality of life, functional capacity, and balance. Method: We studied 17 elders enrolled in the Family Health Strategy (ESF, in Portuguese) at the Centro de Saúde Barreiro, in Belo Horizonte. The assessments were carried out using the Brazilian version of the 36-item Short Form Health Survey (SF -36) of the Medical Outcomes Study, the Berg Balance Scale, and the Katz Index, before and after the treatment plan of 16 twice-weekly sessions of 50 minutes each. Results: Statistical analysis showed significant improvement in balance (p=0.000) and quality of life in the following aspects: functional capacity (p=0.001), physical limitations (p=0.002), pain (p=0.000), overall health (p=0.000), vitality (p=0.001), social (p=0.007) and emotional aspects (p=0.003) and mental health (p=0.000). Significant improvement was found for functional capacity (p = 0.002) measured by Katz. A significance level of 5% was used for all statistical tests. Analyses were carried out using the Statistical Package for Social Sciences (SPSS) software, version 16.0. Conclusion: The preventive physical therapy program significantly improves the quality of life, balance, and functional capacity of older adults and may even contribute to lowering the rates of falls and hospitalizations, possibly reducing health expenditure.


This paper contains the statistics of a survey about the Risk-Free Rate (RF) and the Market Risk Premium (MRP) used in 2020 for 81 countries. We got answers for 87 countries, but we only report the results for 81 countries with more than 6 answers.

Many respondents use for European countries a RF higher than the yield of the 10-year Government bonds. The coefficient of variation (standard deviation/average) of RF is higher than the coefficient of variation of MRP for the Euro countries.

The paper also contains the links to previous years surveys, from 2008 to 2019.

More than fifty respondents provided answers at the beginning of March and later, considering the coronavirus. Most of them increased MRP by 2%.


A new method for the determination of free fibres of chrysotile in contaminated soils is described. The detection limit of 0.5 wt per thousand is reached by an enrichment process of the asbestos fraction of the sample using a standard laboratory elutriator for sedimentation analysis. The analysis of the enriched fraction is performed by X-ray powder diffraction using a conventional instrument. The procedure can be successfully applied to several soils of different nature throughout thermal treatment and removal of possible interferences due to some matrix components. This method is straightforward, routinized and has been especially developed to fulfil the request of public and private institutions for an appropriate quantitative determination of chrysotile free fibres in contaminated soils.


For sequential circuit test pattern generation, the information on invalid states will help greatly on backward justi$cation to reduce the test generation time. This paper proposes three algorithms to find invalid states for sequential circuit test generation. The first two algorithms search the complete set of invalid states by exploring all valid states and reachable states respectively. The first algorithm is efficient for circuits having more invalid states than valid states while the second algorithm is efJicient for circuits having more valid states than invalid states. The third algorithm searches only the invalid states that are required for test generation to stop justification early. Experimental results on ISCAS benchmark circuits show that the algorithm can ident@ invalid states in short time and can help improve test generation significantly in the fault coverage, detection efficiency, and generation time.


Industrial Strength COMPASS (ISC) is a particular implementation of a general framework for optimizing the expected value of a performance measure of a stochastic simulation with respect to integer-ordered decision variables in a finite (but typically large) feasible region defined by linear-integer constraints. The framework consists of a global-search phase, followed by a local-search phase, and ending with a "clean-up" (selection of the best) phase. Each phase provides a probability 1 convergence guarantee as the simulation effort increases without bound: Convergence to a globally optimal solution in the global-search phase; convergence to a locally optimal solution in the local-search phase; and convergence to the best of a small number of good solutions in the clean-up phase. In practice, ISC stops short of such convergence by applying an improvement-based transition rule from the global phase to the local phase; a statistical test of convergence from the local phase to the clean-up phase; and a ranking-and-selection procedure to terminate the clean-up phase. Small-sample validity of the statistical test and ranking-and-selection procedure is proven for normally distributed data. ISC is compared to the commercial optimization via simulation package OptQuest on five test problems that range from 2 to 20 decision variables and on the order of 104 to 1020 feasible solutions. These test cases represent response-surface models with known properties and realistic system simulation problems.


Organic is the order of the day. Consumers show high inclination towards organic food products now a days. In this scenario, a study to analyse the level of influence of factors affecting the buying decisions of organic food products seems to be vital. This study is aimed at identifying and analysing the influence of various factors on the purchase intention of consumers towards organic food products. This research empirically examined the determinants influencing consumers of organic food products by analysing the selection of 100 buyers from Kerala, which is the most literate state of India. Findings of the study reveal that better quality of products that provide the comprehensive wholesomeness and premium price are the most influencing determinants for purchasing organic food products.


Zanthoxylum bungeanum Maxim. (Rutaceae) is a popular food additive and traditional Chinese herbal medicine commonly named HuaJiao in China. This plant is widely distributed in Asian countries. The aim of this paper is to provide a systematic review on the traditional usages, botany, phytochemistry, pharmacology, pharmacokinetics, and toxicology of this plant. Furthermore, the possible development and perspectives for future research on this plant are also discussed. To date, over 140 compounds have been isolated and identified from Z. bungeanum, including alkaloids, terpenoids, flavonoids, and free fatty acids. The extracts and compounds have been shown to possess wide-ranging biological activity, such as anti-inflammatory and analgesic effects, antioxidant and anti-tumor effects, antibacterial and antifungal effects, as well as regulatory effects on the gastrointestinal system and nervous system, and other effects. As a traditional herbal medicine, Z. bungeanum has been widely used to treat many diseases, especially digestive disorders, toothache, stomach ache, and diarrhea. Many traditional usages of this plant have been validated by present investigations. However, further research elucidating the structure-function relationship among chemical compounds, understanding the mechanism of unique sensation, as well as exploring new clinical effects and establishing criteria for quality control for Z. bungeanum should be further studied.


A reading-to-write task is a complex cognitive activity. The aim of this study is to gain insight into the difficulties that advanced learners of Spanish as a foreign language for professional communication purposes experience when they have to perform a reading-to-write task. This insight will help to improve writing instruction and training for this particular type of students. In this study, 19 students of a one-year master's programme in multilingual professional communication (level B2–C1 of the Common European Framework of Reference for Languages, Council of Europe, 2001) were asked to carry out a reading-to-write task in Dutch, their mother tongue, and in Spanish at the beginning of the academic year. This task was repeated at the end of the academic year. On both occasions, the task was writing an informative synthesis of approximately 200–250 words using three digital source texts in Dutch and in Spanish pertaining to different text genres (i.e., a report from the European Union, a website, a newspaper article). The three source texts varied in lexical and syntactical complexity, content, style and discursive characteristics. All written products were evaluated by two independent raters. We found no general improvement in the reading-to-write task between the two moments, neither in the L1 nor in the L2. We did not find an improvement at sentence, text, or discourse level either. We will explore several explanations for this lack of improvement, based on theoretical models of foreign language acquisition and recent empirical writing research.


BACKGROUND
The most used PD fluids contain glucose as a primary osmotic agent. Glucose peritoneal absorption during dwell decreases the osmotic gradient of peritoneal fluids and causes undesirable metabolic consequences. Inhibitors of sodium-glucose co-transporter (SGLT) type 2 are wildly used for the treatment of diabetes, heart and kidney failure. Previous attempts to use SGLT2 blockers in experimental peritoneal dialysis yielded contrasting results. We studied whether peritoneal SGLTs blockade may improve ultrafiltration (UF) via partial inhibition of glucose uptake from dialysis fluids.

METHODS
Kidney failure was induced in mice and rats by bilateral ureteral ligation, and dwell was performed by injection of glucose-containing dialysis fluids. The effect of SGLT inhibitors on glucose absorption during fluid dwell and UF was measured in vivo.

RESULTS
Diffusion of glucose from dialysis fluid into the blood appeared to be sodium-dependent, and blockade of SGLTs by phlorizin and sotagliflozin attenuated blood glucose increment thereby decreasing fluid absorption. Specific SGLT2 inhibitors failed to reduce glucose and fluid absorption from the peritoneal cavity in a rodent kidney failure model.

CONCLUSIONS
Our study suggests that peritoneal non-type 2 SGLTs facilitate glucose diffusion from dialysis solutions, and we propose that limiting glucose reabsorption by specific SGLT inhibitors may emerge as a novel strategy in PD treatment to enhance UF and mitigate the deleterious effects of hyperglycaemia.


III Conclusion Electromagnetic pulse welding (EPW) is an effective way to realize the connection of two different kinds of metal materials via pulsed electromagnetic forces. To improve the welding performance, a new EPW process with a dual-stage coil system was proposed for joining aluminum sheets in this paper, in which one coil is used to generate a pulsed magnetic field with a short pulse width for inducing an eddy current in the aluminum sheet, while the other one is app-lied to generate a background magnetic field with a relatively long pulse width for increasing electromagnetic force acting on the aluminum sheet. The EPW system has been designed and implemented based on the simulation results using the finite element method, with considering the effects of the coil shape, the number of coil turns and the discharge parameters. Finally, experiments are carried out to validate the feasibility of the EPW system, and the microstructure observations of the interfaces show that the welding quality can be effectively improved.


A probability of rupture for WWER-1000 main piping was calculated based on the Failure Assessment Diagram (FAD), treating material properties of welds (the most likely zone for crack growing and its nucleation) and crack morphology parameters as stochastic values. In order to perform probabilistic calculations, Critical Temperature of Brittleness (CTB, WWER's analogue of PWRs transition temperature which used to index the Fracture Toughness curve) and Yield (Ultimate) Strength as well were fitted by normal distribution, based on experimental data taken from the manufacture documentation of Ukrainian Nuclear Power Plants (NPPs). A set of calculations were conducted for Normal Operating conditions (NOC), Safe Shutdown Earthquake (SSE) and several emergency situations like: shaft jamming of a reactor cooling pump and break of the piping's, connected to the considered ones (a set of LOCA events). Based on static and dynamic calculations, the most loaded zones were selected, where the cracks were postulated. Crack opening area was calculated according to original developed procedure, which accounts for membrane and linear stress components through the wall thickness. The Henry-Fauske flow model is used with modified parameters accounting for crack morphology as a normally distributed random variable. It is an important part of analysis, since different crack types have great differences in friction, bend protrusion and flow length parameters. The rupture probabilities for Main Circulating Piping were calculated with accounting for thermal aging effect. It was proven, that crack morphology parameters highly affect the leak rate and its distribution becomes more scattered. Among the mechanical characteristic, a Fracture toughness has more influence rather than Ultimate of Yield strength.


Studies of mortality deceleration sometimes use the order of deceleration between two groups—such as birth cohorts or subpopulations defined by race or sex—to draw conclusions about population heterogeneity. These studies often draw on the fact that between two closed groups, ceteris paribus, the higher-mortality group will decelerate at a younger age. This paper gives a first consideration to the order of deceleration between open groups. I construct a model with a one-way flow from 'healthy' to 'sick' status and, crucially, assume that a subset of the cohort has elevated risk for both sickness and death. Using simulations designed to resemble, in the aggregate, cohorts in the Human Mortality Database, I show that mortality deceleration order in such a cohort is essentially unpredictable because it depends on the interaction between a large number of parameters, some of which are unobserved in empirical data. These results suggest that it may be challenging to extend the study of mortality deceleration to include open groups whose memberships are selected for frailty or robustness, while still drawing meaningful conclusions about population heterogeneity.


The objective of this research is to apply the recently developed fractional cointegration vector autoregressive (FCVAR) model in developing pairs trading model and compare the results to that of the cointegration approach. To the best of our knowledge, there are no papers on fractional cointegration approach to date. Hence, this paper would be the first practical research based on fractional cointegration on futures market.As the focus of this paper in on short-term trading positions, minute intraday interval prices are used to estimate the model and execute the trading strategies. First, we form two portfolios, "FCI" and "CI". FCI is created using fractional cointegration and CI using cointegration approach. Then, using an estimation window of specific length, fractional cointegration test and cointegration test are preformed to verify the existence of fractional cointegration and cointegration relationship between the selected pair respectively. At last, the long-term equilibrium is estimated using Fractional Vector Error Correction Model (FVECM) for FCI and Vector Error Correction Model (VECM) for CI and based on this estimation the trading strategy is implemented. The results show that the fractional cointegration approach yields statistically significant higher returns than the cointegration approach. The number of trades is also lower for fractional cointegration approach, which further contributes to the performance of the strategy. Finally, on a risk-adjusted level, the fractional cointegration approach has a higher Sortino ratio compared to the cointegration approach. Furthermore, window sizes are optimized and the best and worst window sizes for both the cointegration and fractional cointegration estimation window and trading window is reported.


Abstract:Since the mid-1990s, both the Israeli state and Israeli society have been developing and implementing several separate new policies regarding the country's seas. These include the extraction of offshore hydrocarbons; expansion of the navy; massive desalination projects; and several legislative, planning, and zoning initiatives. Put together, these changes amount to a "turn to the sea" that profoundly affects Israel's economy, foreign policy, and military. This article compares this shift to historical precedents, offering Israel as a template for a new, cumulative model that does not conform to the existing narratives of how polities have turned to the maritime domain.


Background The main cause of death in patients with rheumatoid arthritis (RA) is atherosclerotic cardiovascular disease. Speckle Tracking Echocardiography (STE) is an imaging technique that analyses the local and global myocardial function by assessing the myocardial deformation (strain). This technique is useful in addressing early alterations in ischemic pathologies (1,3). Objectives The aim of this study was to analyze if longitudinal strain abnormalities correspond with vascular territories, and compare the results between RA-patients and matched controls. Methods An observational cross-section case-control study was designed. Patients that fulfilled the 1987 ACR and/or 2010 ACR/EULAR classification criteria for RA, were 40–75 years old, with no overlap syndromes and no history of atherosclerotic cardiovascular disease were included. The control group was integrated by age- and sex-matched subjects, with no rheumatologic or cardiovascular diseases. A standard transthoracic echocardiogram was performed by a board-certified echocardiographer. Affection of coronary territories was compared between groups using longitudinal strain by speckle tracking according to the European Society of Cardiology and the American Society of Echocardiography recommendations. Results A total of 53 RA-patients and 24 control subjects were included. Demographic characteristics for each group are shown in table 1. There was no statistical difference in global longitudinal strain between RA-patients and controls (-20.86±2.82 vs -21.19±2.46, p=0.62). Comparison of longitudinal strain values of the three vascular territories evaluated between RA-patients and controls did not reach statistical difference (Table 2).Table 1. Demographic characteristics RA group (n=53) Control group (n=24) p Age, mean ± SD 55.54±9.11 52.81±6.61 0.172 Women, n (%) 51 (96.2) 26 (96.3) 0.988 Body Mass Index, mean ± SD 27.53±5.85 28.05±4.66 0.956 Hypertension, n (%) 18 (33.96) 5 (18.5) 0.149 Type 2 Diabetes mellitus, n (%) 7 (13.2) 4 (14.8) 0.844 Conclusions Contrary to previous published evidence (1, 2), there was no statistical difference in global longitudinal strain between RA patients and controls. Coronary territories are not affected in RA patients in comparison with controls. Further studies with a larger cohort are necessary to determine the usefulness of strain in the evaluation of subclinical cardiovascular disease. References Fine et al. Evaluation of myocardial function in patients with rheumatoid arthritis using strain imaging by speckle-tracking echocardiography, Ann Rheum Dis. 2014 Oct;73(10):1833–9. Sitia S, Tomasoni L, Cicala S, et al. Detection of preclinical impairment of myocardial function in rheumatoid arthritis patients with short disease duration by speckle tracking echocardiography. Int J Cardiol 2012;160:8–14. Batir et al, Herz. 2015 Jun;40(4):669–74. Preclinical impairment of myocardial function in rheumatoid arthritis patients. Detection of myocardial strain by speckle tracking echocardiography. Disclosure of Interest None declared


We develop a numerical model to predict the volume and distribution of gas hydrate in marine sediments. We consider the environment of a deep continental margin where sedimentation adds organic material to the region of hydrate stability. Conversion of the organic material to methane by bacteria promotes hydrate formation and depletes the supply of organic carbon. We derive mass balance equations for the volume of hydrate and gas bubbles in the sediments and account for the changing concentration of dissolved methane and salts in the pore fluid. The effects of sediment compaction and the associated fluid flow are explicitly modeled. Allowances for deeper sources of fluid are also described, though we focus on the case of an idealized passive margin where carbon is input solely through sedimentation. The numerical calculations indicate that the key parameters in this model are the rate of sedimentation, the quantity and quality of the organic material, and a rate constant that characterizes the vigor of biological productivity. Model predictions for conditions that are representative of the Blake Ridge are compared with observations from Ocean Drilling Program Leg 164. We obtain a very good match to the observed chlorinity profile, including the region below the stability zone, without invoking any extraneous sources of freshening. We also predict that hydrate is unlikely to occupy more than 7% of the pore volume, in good agreement with observed estimates.


Wool is a natural fibre with a unique amalgamation of properties that are exploited in garment industry. The wool industry, in particular the production of fine wool, has a notable role in world trade and the price of the wool is dependent on quality. Accordingly, wool characteristics have direct impact on wool prices set by processors and industry. These properties can particularly benefit the wearer of the garment during exercise. There are different factors affecting wool quality parameters both with direct and indirect involvement. The environmental and genetics are the main factors affecting quality and quantity of wool from sheep. Infections related to skin and parasitic infestations have direct influence on the quality of wool. Breed or genotype is one of the main genetic factors that influences the product and productivity as well as quality of wool from sheep that is fleece from different sheep breeds is different in its both physical and chemical characteristics. Hormonal changes in relation to sex of sheep also have effect on the wool quality traits. The main objective of this review was to define and explore key wool characteristics, such as staple length, number of crimp, fibre type, fibre diameter, wool wax and scouring yield in regards to quality and interventions approaches for improving. In most of studies, non-genetic factors such as age, season, shearing period, shearing frequency and nutrition have a significant effect on traits viz. staple length, wool wax, scouring yield, fibre diameter and for other traits as well. Conducting a research on wool quality characteristics is an operative way of defining and differentiating the quality of wool. Acquiring knowledge of the wool quality characteristics can help to manage the end use products, consumers comfort and processing intensity. Therefore, an understanding of the factors affecting physical and chemical properties of wool traits is important to improve the quality of wool through genetics and management interventions. This article reviews some important quality attributes of wool for the product and productivity development and value addition.


The lagoon of sweet dreams and only one (long) silence. Hugo Pratt has been the first cartoonist able to highlight both dialogues and silences into adventure. In a short tale belonging to the first series of Corto Maltese's adventures – the charachter is present only in a few frames, at the very beginning and at the end – Pratt shows to the reader the last moments of an English sargent escaped from the First World War. His delirium is coincident with the accomplishment of all his desires. The penultimate page proposes three close-up of three different characters (Corto Maltese is the last one) looking towards us, silently. For the comics' history these three frames are memorable, marking the passage from dream to reality, from death to life.


The presence of the E2 region of HPV 16 was determined by the polymerase chain reaction in biopsy samples with different histopathological diagnoses. The absence of the E2 gene was observed in 17 of 30 cases examined. The E2 deletions were not confined exclusively to invasive carcinomas or to integrated viral forms. In the majority of cases, the course of cervical lesions was consistent with the state of the E2 gene.


Wireless sensor networks provide occupational health experts with valuable information about the distribution of air pollutants in an environment. However, especially low-cost sensors may produce faulty measurements or fail completely. Consequently, not only spatial coverage but also redundancy should be a design criterion for the deployment of a sensor network. For a sensor network deployed in a steel factory, we analyze the correlations between sensors and build machine learning forecasting models, to investigate how well the sensor network can compensate for the outage of sensors. While our results show promising prediction quality of the models, they also indicate the presence of spatially very limited events. We, therefore, conclude that initial measurements with, e.g., mobile units, could help to identify important locations to design redundant sensor networks.


Philip Kotler identified the term "marketing" with two different but related processes; the first dealing with "the search for and stimulation of buyers" and the second with "the physical distribution of goods". The reason for superior international marketing performance by certain companies may be the result of a small number of correct strategic decisions, or of being in the right industry at the right time and being able to meet market demands. Continual high international marketing performance, however, is more likely to be the result of exceptional management control to overcome the problems of both the search and stimulation of overseas markets and the growing commitment successfully to feed those markets with the goods through a planned physical distribution pattern. International physical distribution management is not merely a marketing support system, but it is an integral part of the marketing mix which helps create and develop the international marketing process. Even though physical distribution does not portray the glamour associated with international marketing, it should not be forgotten as a part of the marketing mix. However, in the future, international marketing success may depend more and more upon the efficiency and practices employed to ensure economic physical distribution of goods especially as competition intensifies from developed and developing nations.


Data characterising the contribution of electron transfer processes to the stereochemistry of reactions of organic compounds are discussed and the stereochemical changes accompanying electron transfer are analysed. It is shown that the decrease of the barrier to rotation in electron transfer facilitates the cis–trans isomerisation of ethylenes and an increase of the difference between the energies of the rotational isomers of certain radical-ions relative to neutral molecules decreases the rate of mutual rotation. The influence of the formation of ion pairs by the anionic and cationic components of the radical-ion salts on the stabilisation of unusual geometrical forms of the molecule is discussed. The conversion of cyclopolyenes into ionic forms with a ring current of delocalised electrons, which fixes the ring atom in a single plane, is considered as a special case of electron transfer. The chemical and physical properties of cyclo-octatetraene, azocine, and their ionic forms are compared. The bibliography includes 143 references.


Objectives: Anatomical brain asymmetries in cadaveric human brains are not well defined in the literature. Therefore, the present study was undertaken to observe the variations in right and left cerebral hemispheres using various parameters. Methods: Twenty eight adult human brains irrespective of sex were taken for the present study. Various measurements of cerebral hemisphere including fronto-occipital length, cerebral width, Sylvian fissure length and distance between anterior Sylvian point to inferior Rolandic point were taken. These measurements were taken by Vernier calipers. Different configuration of the anterior ascending and anterior horizontal ramus of the Sylvian fissure were also examined as U-shaped, V-shaped and Yshaped. The presence or absence of triangular sulcus located within pars triangularis was also observed. Results: The fronto-occipital length was longer on right side while the cerebral width and Sylvian fissure length were more on left side. These values were significant statistically. The configuration of the anterior ascending and anterior horizontal ramus of the Sylvian fissure was V-shaped in maximum number of hemispheres followed by U-shaped. The triangular sulcus was noted in thirty hemispheres i.e. 16 right and 14 left. Conclusions: Hemispheres of the brain are not identical and functional asymmetries have an underlying anatomical basis.


Electronic Commerce is all the rage these days. Current challenge of Electronic Commerce for suppliers is to allow building dynamic supply link and to meet various and wide needs for the customers, furthermore to build more reasonable electronic market places at run time. In this article we aim to provide a common reference infrastructure contains an instantiation of the I S 0 7 layer model for Electronic Commerce and uses modem software engineering design paradigms. A way of identihing distributed building primitives for large-scaled integration and multi-enterprise transactions is shown.


. The quest for efficiency is becoming more and more of an obligation for both public administrations and for-profit enterprises. In our article, we tried to question the management system of local authorities, particularly at the most outsourced level, that of municipalities. To this end, we conducted a comprehensive method using qualitative data gathering techniques (both a semi directive interview and secondary data analysis) to question this management system. We assessed their performance and, subsequently, suggested avenues that can be qualified as alternatives in favor of the efficiency of these communities and the improvement of their productivity


Sixty-three structurally diverse compounds were investigated to statistically model the brain-blood partitioning of organic solutes using theoretically computed molecular descriptors and multivariate statistics. The program MolSurf was used to compute theoretical molecular descriptors related to physicochemical properties such as lipophilicity, polarity, polarizability, and hydrogen bonding. The multivariate Partial Least Squares Projections to Latent Structures (PLS) method was used to delineate the relationship between the brain-blood partitioning of organic solutes and the theoretically computed molecular descriptors. Good statistical models were derived. Properties associated with polarity and Lewis base strength had the largest impact on the blood-brain partitioning and should be kept to a minimum to promote high partitioning. The absence of atoms capable of hydrogen bonding interactions as well as high lipophilicity and the presence of polarizable surface electrons, i.e., valence electrons, were also found to promote high brain-blood partitioning. The results indicate that theoretically computed molecular MolSurf descriptors in conjunction with multivariate statistics of PLS type can be used to successfully model the brain-blood partitioning of organic solutes and hence differentiate drugs with poor partitioning from those with acceptable partitioning at an early stage of the preclinical drug-discovery process.


Message passing is a fundamental procedure for graph neural networks in the field of graph representation learning. Based on the homophily assumption, the current message passing always aggregates features of connected nodes, such as the graph Laplacian smoothing process. However, real-world graphs tend to be noisy and/or non-smooth. The homophily assumption does not always hold, leading to sub-optimal results. A revised message passing method needs to maintain each node's discriminative ability when aggregating the message from neighbors. To this end, we propose a Memory-based Message Passing (MMP) method to decouple the message of each node into a self-embedding part for discrimination and a memory part for propagation. Furthermore, we develop a control mechanism and a decoupling regularization to control the ratio of absorbing and excluding the message in the memory for each node. More importantly, our MMP is a general skill that can work as an additional layer to help improve traditional GNNs performance. Extensive experiments on various datasets with different homophily ratios demonstrate the effectiveness and robustness of the proposed method.


A 12-week feeding trial was conducted to estimate the effects of supplemented amino acids (lysine and methionine) with different dietary protein levels on growth, haematology and liver histology in meagre (Argyrosomus regius) at two different sizes: fingerling (15.2 g) and juvenile (44.4 g). Six practical diets were prepared, and three of these practical diets were formulated with 40 (P40), 44 (P44) and 48% (P48) crude protein without supplementation of amino acids. Other three diets having same protein levels were supplemented with lysine and methionine (P40AA, P44AA and P48AA) to bring these amino acids level up to that estimated to be at the least in the 48% protein diet. Final mean weight (FMW) and specific growth rate (SGR) of P48AA in fingerlings were higher than that of 40AA. According to FMW and SGR of juveniles, there was interaction found between dietary protein levels and the supplementation of amino acids. The FMW and SGR of meagre fed P44AA were higher than that of fish fed the other diets, except fish fed the P48. Economic profit index, packed cell volume and haemoglobin for juvenile meagre were significantly improved with the dietary protein level and amino acid supplementation. The liver tissues of the P48 group in both sizes displayed better structure compared with the other groups. In conclusion, dietary crude protein content of practical diets for juvenile meagre could be reduced from 48% to 44% by adding essential amino acids with an enhancement in growth, health and economic profit.


Metallocenes, whether using a cocatalyst or not, act as catalysts in ethylene polymerization. The positive charge on the transition metal of a metallocene might have an important role in polymerization as an active site in our model approach. Using semiempirical calculations in the absence of cocatalyst, we show one of the possibilities that the positive charge on a metallocene might be more easily transferred through the Cp ring of a ligand to the ethylene than to transfer directly from the transition metal to the ethylene. In these calculations, the charge on titanium in an eight C 2 H 4 system is transferred and a polymer chain is produced. This reaction takes place only when ethylenes are arranged in a particular direction with respect to the ring, but does not take place for ethylenes near Ti or Cl atoms. The same mechanism is shown for a metallocene ligand which is sterically hindered or where the Cp ring is replaced by fluorenyl. These results suggest an entirely new polymerization mechanism in the absence of a cocatalyst in which the Cp ring is the active site.