Copper homeostasis mechanisms are essential for microbial adaption to changing copper levels within the host during infection. In the opportunistic fungal pathogen Cryptococcus neoformans (Cn), the Cn Cbi1/Bim1 protein is a newly identified copper binding and release protein that is highly induced during copper limitation. Recent studies demonstrated that Cbi1 functions in copper uptake through the Ctr1 copper transporter during copper limitation. However, the mechanism of Cbi1 action is unknown. The fungal cell wall is a dynamic structure primarily composed of carbohydrate polymers, such as chitin and chitosan, polymers known to strongly bind copper ions. We demonstrated that Cbi1 depletion affects cell wall integrity and architecture, connecting copper homeostasis with adaptive changes within the fungal cell wall. The cbi1Δ mutant strain possesses an aberrant cell wall gene transcriptional signature as well as defects in chitin and chitosan deposition. These changes are reflected in altered macrophage activation and changes in the expression of specific virulence-associated phenotypes. Furthermore, using Cn strains defective in chitosan biosynthesis, we demonstrated that cell wall chitosan modulates the ability of the fungal cell to withstand copper stress. In conclusion, our data suggest a dual role for the fungal cell wall, in particular the inner chitin / chitosan layer, in protection against toxic levels of copper and providing a source of metal ion availability during copper starvation. Given the previously described role for Cbi1 in copper uptake, we propose that this copper-binding protein is involved in shuttling copper from the cell wall to the copper transporter Ctr1 for regulated microbial copper uptake. Author summary Microorganisms must be equipped to readily acquire essential micro-nutrients like copper from nutritionally poor environments while simultaneously shielding themselves from conditions of metal excess. We explored mechanisms of microbial copper homeostasis in the human opportunistic fungal pathogen Cryptococcus neoformans (Cn) by defining physiological roles of the newly described copper-binding and release protein Cn Cbi1/Bim1. Highly induced during copper limitation, Cbi1 has been shown to interact with the high-affinity copper transporter Ctr1. We defined Cbi1-regulated changes in the fungal cell wall, including controlling levels of the structural carbohydrates chitin and chitosan. These polysaccharides are embedded deeply in the cell wall and are known to avidly bind copper. We also defined the host immunological alterations in response to these cell wall changes. Our data suggest a model in which the fungal cell wall, especially the chito-oligomer layer, serves as a copper-binding structure to shield the cell from states of excess copper, while also serving as a copper storage site during conditions of extracellular copper depletion. Given its ability to bind and release copper, the Cbi1 protein likely shuttles copper from the cell wall to copper transporters for regulated copper acquisition.


Material Requirements Theory (MRP Theory) combines the use of Input-Output Analysis and Laplace transforms, enabling the development of a theoretical background for multi-level, multi-stage production-inventory systems together with their economic evaluation, in particular applying the Net Present Value (NPV) principle. The time scale may be continuous ("bucketless" in MRP terminology) or discrete. Since the average cost measure may be viewed as an approximation of NPV, the theory may be applied to cases, when average costs are preferred as the objective function.


In image transmission, channel noise causes severe degradation in the quality of received images. Thus graceful degradation mechanism and error correction capability should be implemented in accordance with various image transmission scenarios. This paper presents a trial to address such a problem. In particular, the effect of error control coding (ECC) is investigated to protect the coded image quality against inevitable channel noise. Simulation results show that error control coding guarantees to receive images with the same PSNR as in the noiseless case when bit error rate (BER) is lower than 5/spl times/10/sup -3/.


An 86-year-old woman, 4 days post-operative following a right-sided Austin-Moore arthroplasty, reported abdominal pain around a known umbilical hernia and became increasingly confused. A diagnosis of incarcerated umbilical hernia was made. At surgery, on entering the peritoneal cavity, bile was immediately noted. The operation was converted to a laparotomy and a perforation was noted in the gallbladder. An open cholecystectomy was performed. Macroscopically the gallbladder was perforated in multiple places, was thin walled and did not contain gallstones. This case demonstrates the difficulty in diagnosing an apparently spontaneous gallbladder perforation in a cognitively frail patient.


Various problems, involving money, space, personnel, and their relationship to the hospital administration, can be associated with the establishment of a Burn Unit. However, these problems can be overcome. During the creation of a Burn Unit, consultation regarding the design features of the unit is particularly important.


The surface science of heterogeneous metal catalysis uses model systems ranging from single crystals to monodispersed nanoparticles in the 1-10 nm range. Molecular studies reveal that bond activation (C-H, H-H, C-C, CO) occurs at 300 K or below as the active metal sites simultaneously restructure. The strongly adsorbed molecules must be mobile to free up these sites for continued turnover of reaction. Oxide-metal interfaces are also active for catalytic turnover. Examples using C-H and CO activation are described to demonstrate these properties. Future directions include synthesis, characterization, and reaction studies with 2D and 3D monodispersed metal nanoclusters to obtain 100% selectivity in multipath reactions. Investigations of the unique structural, dynamic, and electronic properties of nanoparticles are likely to have major impact in surface technologies. The fields of heterogeneous, enzyme, and homogeneous catalysis are likely to merge for the benefit of all three.


This study aims to determine the digital literacy competence of students in the city of Bandung. This study used descriptive qualitative method. The data collection technique used was semi-structured interviews involving 10 informants from 5 universities in the city of Bandung. The results showed that some students in the city of Bandung generally have digital literacy competencies which consist of: 1) the ability to understand internet searching, namely using search engines to find information, understanding the internet as a source of information, connecting and using the internet to carry out several activities; 2) competence in how hyperlinks work, even though they lack the meaning of hypertext; 3) content evaluation competence, they are able to understand the characteristics of websites that are used as references, cross-check the information they get and use FAQs on a website to help them get information; 4) competence in compiling knowledge by using keywords to facilitate the search for information, utilizing other sources of information other than the internet


Lower abdominal, perineal, and groin (LAPG) reconstruction may be performed in a single stage. Anterolateral thigh (ALT) flaps are preferred here and taken as fasciocutaneous (ALT‐FC), myocutaneous (ALT‐MC), or vastus lateralis myocutaneous (VL‐MC) flaps. We aim to present the results of reconstruction from a series of patients and guide flap selection with an algorithmic approach to LAPG reconstruction that optimizes outcomes and minimizes morbidity. Lower abdomen, groin, perineum, vulva, vagina, scrotum, and bladder wounds reconstructed in 22 patients using ALT flaps between 2000 and 2013 were retrospectively studied. Five ALT‐FC, eight ALT‐MC, and nine VL‐MC flaps were performed. All flaps survived. Venous congestion occurred in three VL‐MC flaps from mechanical cause. Wound infection occurred in six cases. Urinary leak occurred in three cases of bladder reconstruction. One patient died from congestive heart failure. The ALT flap is time tested and dependably addresses most LAPG defects; flap variations are suited for niche defects. We propose a novel algorithm to guide reconstructive decision‐making. © 2014 Wiley Periodicals, Inc. Microsurgery 36:104–114, 2016.


Purpose
The purpose of this paper is to investigate the role of gender in the relationships between employee's work experience and their chances of obtaining a job promotion.

Design/methodology/approach
Five hundred middle to lower management Pakistan employees from service industries were surveyed. Measures used to obtain data included work experience, job promotions and gender. Gender was dummy coded. Moderation analyses via SPSS was used to investigate the moderating effect of gender in the relationship between employee's work experience and job promotions.

Findings
The results indicated that work experience was positively associated with job promotion. However, the results indicated that gender fully moderated the relationship between work experience and job promotion. Specifically, female employees were less likely to get promoted compared to male employees despite having similar work experiences.

Research limitations/implications
Drawing together the human capital theory, social role theory and cultural factors, this study highlighted the socioeconomic/cultural barriers' impact on Pakistani women's career ascendance.

Practical implications
There is a lack of empirical evidence about career ascendance among Pakistani women. Therefore, the aim of the present study is to conduct and provide empirical evidence so that relevant agencies within Pakistan can develop more gender-equitable promotional policies and processes.

Originality/value
This study responded to the call for more empirical investigation of career ascendancy among women in developing countries. While this issue has been discussed in many developed western countries, there is a lack of empirical evidence in Muslim Pakistan.


An analysis of a small sample of countries shows that the higher the level of termsof-trade risk that a nation faces in international markets, the more likely it is to increase barriers. The analysis also shows that the greater the availability of social insurance programs mounted by a nation's government, the less likely it is to block free trade. In comparison with the small open economies of Western Europe, therefore, developing countries may remain protectionist because they lack the resources to mount internal programs of transfer payments as a means of coping with risk from international markets.


In many disordered systems such as supercooled liquids the relaxation function does not decay exponentially with time. In this paper, it is shown from a consideration of the initial conditions that a system of identical molecules, each of which has the same non-exponential relaxation function, must be inhomogeneous. As a result, the relaxation function for the system is not the same as that of an individual molecule, contrary to what is often assumed. As an example, the general formulae are applied to a simple model system in which the dielectric relaxation function of the individual molecules is of the stretched exponential form. It is found that while the dielectric relaxation of the system can be well approximated by a function of this form, its stretching parameter and relaxation time differ from those for the individual molecules.


Some angiotensin receptor (AR) blockers interfere with the renal chloride channel (ClC-K), which plays an important role in urine concentration. Identifying ligands targeting this channel, whether activating or blocking, is highly desirable because it could open the way for interventions that modulate their activity. In this study, the Asinex (BioDesign) complete library was screened to identify a compound with favorable physicochemical and pharmacokinetic properties, which have both AR blocking and ClC-Ka-modulating activities to present it as a novel potential oral candidate which could be useful for treatment of salt-sensitive hypertension without major ClC-K affection. A compound, N-{[4-Hydroxy-1-(2-methyl-1,6-naphthyridin-4-yl)-4-piperidinyl]methyl}-N-methyl-L-lysinamide (N-HyMenatPimeMelly) (Chem Spider ID 68416221), was identified as a potent potential oral ligand of the renin-angiotensin system (RAS) and ClC-Ka with docking scores ranging from -10.978 to -7.324 with the four selected proteins (4YAY: AR type 1, 2PFI: Cytoplasmic domain of ClC-Ka, 6JOD: AR type 2 and 6M0J: Angiotensin-converting enzyme 2). The protein-ligand complex was used to perform molecular dynamics (MD) simulation for 100 ns. The QikProp and SwissADME tools' results showed that the compound has ADME/T and drug-likeness properties, which are within the permissible ranges for 95% of known drugs. The density functional theory (DFT) analysis and MD simulation extended the study toward computational validation. Throughout the study, N-HyMenatPimeMelly has shown good interactions and stable performance in MD simulation and DFT analysis. The whole analysis has produced promising results, and N-HyMenatPimeMelly can be treated as a novel potential RAS and ClC-K oral ligand, however, experimental validation is needed before human use.Communicated by Ramaswamy H. Sarma.


Significance Sickle cell anemia (SCA) is a common monogenic disorder associated with significant morbidity and mortality and a high incidence of unexplained sudden death in young adults. With the prevention of infections, there is an increasing appreciation for cardiopulmonary complications and a cardiac phenotype that cannot be solely attributed to chronic anemia. We used mouse models of SCA and iron-deficient anemia to show distinct functional, pathological, ultrastructural, and molecular cardiac features causing a unique restrictive cardiomyopathy in SCA that predisposed the myocardium to electrophysiological abnormalities and sudden death. This is a comprehensive longitudinal analysis in preclinical mouse models that unifies the previously reported diverse cardiac phenotypes in SCA, and opens new avenues for early diagnostics and targeted therapies for human SCA-related cardiac disease. Cardiopulmonary complications are the leading cause of mortality in sickle cell anemia (SCA). Elevated tricuspid regurgitant jet velocity, pulmonary hypertension, diastolic, and autonomic dysfunction have all been described, but a unifying pathophysiology and mechanism explaining the poor prognosis and propensity to sudden death has been elusive. Herein, SCA mice underwent a longitudinal comprehensive cardiac analysis, combining state-of-the-art cardiac imaging with electrocardiography, histopathology, and molecular analysis to determine the basis of cardiac dysfunction. We show that in SCA mice, anemia-induced hyperdynamic physiology was gradually superimposed with restrictive physiology, characterized by progressive left atrial enlargement and diastolic dysfunction with preserved systolic function. This phenomenon was absent in WT mice with experimentally induced chronic anemia of similar degree and duration. Restrictive physiology was associated with microscopic cardiomyocyte loss and secondary fibrosis detectable as increased extracellular volume by cardiac-MRI. Ultrastructural mitochondrial changes were consistent with severe chronic hypoxia/ischemia and sarcomere diastolic-length was shortened. Transcriptome analysis revealed up-regulation of genes involving angiogenesis, extracellular-matrix, circadian-rhythm, oxidative stress, and hypoxia, whereas ion-channel transport and cardiac conduction were down-regulated. Indeed, progressive corrected QT prolongation, arrhythmias, and ischemic changes were noted in SCA mice before sudden death. Sudden cardiac death is common in humans with restrictive cardiomyopathies and long QT syndromes. Our findings may thus provide a unifying cardiac pathophysiology that explains the reported cardiac abnormalities and sudden death seen in humans with SCA.


Monomeric LiPhNNPhSiMe3.2Et2O was obtained by deprotonation of PhHNNPhSiMe3 with BuLi in the presence of Et2O. Reaction of NaN(SiMe3)2 with PhHNN(SiMe3)2 in a C6H6/THF mixt. provided monomeric NaPhNN(SiMe3)2.3THF, or NaPhNN(SiMe3)2.THF using a small amt. of THF. THF can be replaced by Et2O or tBuOMe to give 1:1 solvates. These assoc., forming chains in the solid state via hn coordination (n = 2, 3) of their Ph groups to the Na centers of adjacent mols. In contrast, not only deprotonation but also desilylation occurs on reaction of NaN(SiMe3)2 with PhHNNPhSiMe3 or of NaNH2 with Me3SiHNNPh2. The latter reaction results in the formation of hexameric (NaHNNPh2)6, which adopts a face-sharing double-cubane structure. [on SciFinder (R)]


Women with type 1 diabetes are at increased risk of preeclampsia, and microalbuminuria (urinary albumin excretion of 30-300 mg/24 hours) has proved to be a reliable marker for preeclampsia in these women. Because collecting a 24-hour urine sample is cumbersome and time-consuming, an alternative test would be welcome. One approach might be to estimate the albumin-to-creatinine ratio in random urine samples. Whether this is feasible was determined in 119 women with type 1 diabetes who were seen before 14 weeks gestation and were asked to provide 2 24-hour urine collections and 2 random samples during gestational weeks 7 and 22. Albumin was estimated by an enzyme-linked immunosorbent assay. Microalbuminuria was defined as an albumin to creatinine ratio of 2.5 mg/mmol or more, and nephropathy was defined as a ratio exceeding 25 mg/mmol (210 μg/mg creatinine). Normoalbuminuria was documented in 103 women, whereas 7 had microalbuminuria and 9 had macroalbuminuria/ nephropathy. There were no significant group differences in age, duration of diabetes, or HbA 1c . Median urinary albumin excretion was 8, 66, and 677 mg/24 hours, respectively, in the 3 groups. The 24-hour urinary albumin excretion correlated positively with the albumin-to-creatinine ratio in random urine samples (P <.001). All but one of 16 women excreting more than 30 mg albumin in 24 hours had a ratio exceeding 2.5 mg/mmol, a sensitivity of 94%. However, all 9 women excreting more than 300 mg albumin in 24 hours had a ratio above 25.0 mg/mmol for a sensitivity of 100%. All 103 women with normoalbuminuria had a ratio less than 2.5 mg/mmol for a specificity of 100%. Positive and negative predictive values for a low ratio were 100% and 99%, respectively. The day-to-day coefficient of variation was 40% for 24-hour urine collections and 49% for random urine samples. The investigators believe that measuring the albumin-to-creatinine ratio in 2 random urine samples is a very sensitive and specific means of screening for micro- and macroalbuminuria in pregnant women with type 1 diabetes. It is an acceptable alternative to collecting 24-hour urine samples.


This article explores the religious and political identities of feminist Witches through a discussion of the way feminist Witchcraft constructs prehistoric Goddess societies as colonized by patriarchal societies and early modern European witch hunts as maintaining that colonization. Feminist Witches often use colonial and postcolonial language to indicate the relationship between patriarchal religion(s) and/or system(s) and that of women and women-centered religious systems. Thus, though often problematic, colonialism stands in for patriarchy in many instances; similarly, postcolonialism stands in for the shaping of a new future in which feminist Witches are engaged. This article explores how feminist Witchcraft uses the metaphor of colonialism and postcolonialism with an aim to understand how feminist Witches understand their own identities both as members of a marginal new religious movement and as predominantly white women in a postcolonial setting.


The article summarizes the experience in developing, implementing and effectiveness evaluating of the sexually transmitted infection prevention program in the subpopulation of injecting drug users in St. Petersburg, Russia. The preventive intervention was aimed to correct behaviors leading to infection and was based on a multidisciplinary patient-centered approach. Long-term medical, social and psychological support of injecting drug users, combined with the group training sessions based on the peer-to-peer model has allowed to reduce their injecting and sexual risk, as well as to decrease the HIV infection incidence in the intervention group 1.84 times against the control group.


Analyzing and handling the inconsistency in requirements is critical to the development of complex software systems. How to solve this problem directly influences the quality of requirements specification, as well as the final software production. Based on a common-recognized management framework of requirements inconsistency, this paper summarizes representative researches on this topic. The main aim is to get a comprehensive understanding of the current techniques and methods of inconsistency management. Finally, the paper also identifies some issues which are still open to further research.


In heavy ion reactions at energies around (1-2)A GeV the measured K- yields appear rather high as compared to pp collisions as shown by the KaoS Collaboration. Employing quantum molecular dy-namics simulations, we show that this is caused by the fact that the dominant production channel is not BB-->BBK+K- but the mesonic Lambda(Sigma)pi-->K-B reaction. Because the Lambda (Sigma) stem from the reaction BB-->Lambda(Sigma)K+B, the K+ and the K- yield are strongly correlated, i.e., the K(-)/K(+) ratio occurs to be nearly independent of the impact parameter as found experimentally. The final K- yield is strongly influenced by the K+N [due to their production via the Lambda(Sigma)] but very little by the K-N potential.


OBJECTIVE
To investigate the infection of HHV-8 virus in free blood donors in Wuhan.

METHODS
Whole blood samples were collected from 450 free blood donors in Wuhan, and the genomic DNA extraction and serum collection were performed respectively. And then, the positive rate of HHV-8 was detected by PCR and ELISA, the positive detection rates were compared between them. Finally, HHV-8 ORFK1 gene was cloned by PCR in the positive samples, and the HHV-8 ORFK1 gene th was genetyped through sequencing analysis, homology comparison and phylogenetic tree construction.

RESULTS
25 and 23 cases of positive samples were detected by PCR and ELISA, their positive rate were 5.56% and 5.11% respectively, and without statistically significant difference using χ2 test analysis (P > 0.05). Based on the results of ORFK1 gene cloning and sequence analysis in 23 positive samples, 15 samples C subtype of had HHV-8 ORFK1 gene, and 8 cases had A subtype had HHV-8 ORFK1 gene.

CONCLUSION
There is a certain percentage of HHV-8 infection in the free blood donors in Wuhan. It is suggested to increase the HHV-8 virus screening for free blood donors, so as to ensure the quality of blood.


Hemophilic pseudotumor (HP) is rare, seen in 1–2% of patients with hemophilia, and is extremely uncommon in the mandible. A 6‐year‐old boy with moderate hemophilia A presented to our hospital with left mandibular swelling. Based on clinical and radiological findings, a tentative diagnosis of HP was made. After factor VIII administration, the lesion was curetted and HP was confirmed on histopathology. The patient was treated with twice‐weekly factor VIII until the lesion had completely resolved and bone had regenerated at 1 year. The best treatment for HP is not established; however, appropriate initial treatment and postoperative prophylaxis are effective.


ABSTRACT Direct-patternable lanthanum substituted lead zirconate titanate (PLZT) films were prepared by sol-gel technique using orth-nitrobenzaldehyde as a photosensitive agent. PLZT films with various La concentration were formed on Pt(111)/Ti/SiO2/Si(100) substrate for direct-patterning of PLZT films and ferroelectric properties measurement. A well-defined and direct-patterned PLZT film was obtained and the improvement of leakage current density, fatigue resistance and dielectric constant with increased substitution of La in PLZT film were observed especially with 4 mol% La doped PLZT film. From this result, we confirmed that direct-patternable PLZT film is suitable for application in micro device.


Cancer mortality rates are undergoing a global downward trend; however, metastasis and relapse after surgery and adjuvant treatments still correlate with poor prognosis and represent the most significant challenges in the treatment of this disease. Advances in genomics, metabolomics, and proteomics are improving our understanding regarding cancer metabolic diversity, resulting in detailed classifications of tumors and raising the effectiveness of precision medicine. Likewise, the growing knowledge of interactions between nutrients and the expression of certain genes could lead to cancer therapies based on precision nutrition strategies. This review aims to identify the recent advances in the knowledge of the mechanistic role of bioactive phytochemicals in foodstuffs in tumor progression, metastasis, and chemo-resistance in order to assess their potential use in precision nutrition therapies targeting relapse in lung, breast, colon, and prostate cancer, and leukemia. A considerable number of bioactive phytochemicals in foodstuffs were identified in the literature with proven effects modulating tumor growth, progression, and metastasis. In addition, the use of foodstuffs in cancer, and specifically in relapse therapies, is being reinforced by the development of different formulations that significantly increase the therapeutic efficiency of these products. This can open the possibility for testing combinations of bioactive phytochemicals with cancer relapse treatments as a potential prevention strategy.


Cancer, one of the leading health concerns for humans, is by no means a human‐unique malady. Accumulating evidence shows that cancer kills domestic and wild animals at a similar rate to humans and can even pose a conservation threat to certain species. Assuming that each physiologically active and proliferating cell is at risk of malignant transformation, any evolutionary increase in the number of cells (and thus body mass) will lead to a higher cancer frequency, all else being equal. However, available data fail to support the prediction that bigger animals are affected by cancer more than smaller ones. The unexpected lack of correlation between body size (and life span) and cancer risk across taxa was dubbed Peto's paradox. In this perspective, several plausible explanations of Peto's paradox are presented, with the emphasis on a largely underappreciated relation of cell size to both metabolism and cell division rates across species, which we believe are key factors underlying the paradox. We conclude that larger organisms have bigger and slowly dividing cells with lower energy turnover, all significantly reducing the risk of cancer initiation. Solving Peto's paradox will enhance our understanding the evolution of cancer and may provide new implications for cancer prevention and treatment.


In this paper, a real-time H.264/AVC baseline profile decoder is implemented on independent platform. Computationally intensive modules in the reference decoder are optimized for various hardware platforms. Especially, a fast group-based CAVLC entropy decoding algorithm is provided in detail, and several strategies are discussed from software optimization opinion. The experiments show that the speed of our developed software-based decoder is 3 times faster than that of the H.264/AVC reference decoder. The maximum decoding speed of 74 fps for CIF sequence is achieved on Intel Pentium 4 processor, with the same video quality as the reference decoder.


Restricted fetal growth and development is supported by the adequacy of several micronutrients, andmostly by iron, zinc, calcium, folate and B12 vitamin. This study aims to evaluate the maternal micronutrientstatus from dietary intake and blood sample. A cross-sectional study as part of the micronutrient interventionstudy was carried out in 143 healthy pregnant women during their first visit to the two maternity clinics inJakarta Indonesia (August 2013 – July 2014). Twenty-four hour dietary recall and semi-quantitative foodfrequency questionnaire were used to collect micronutrient intake data, while standard laboratory procedureswere applied to analyze micronutrient status from the blood sample. The dietary assessment data showedinsufficiency of iron, zinc, calcium, vitamin D, folate and vitamin B12 intake (less than its RDA) among 88.8%,95.1%, 97.9%, 100%, 90% and 78.3%, respectively. In relation iron status, 11.2% of the subjects were anemicand 20.3% had low ferritin level. Zinc deficient was found among 35% of the subjects. Deficiency of calciumand vitamin D were found among 25.2% and 90.2% of the subjects, respectively. Furthermore, deficiency ofboth folate and vitamin B12 were found to be 2.8%. Nutrition counseling and education, and the provision ofmulti-micronutrient fortified food as well as multi-micronutrient supplement specifically designed for mothersshould be started in the earliest time, i.e. starting from the peri-conception period. Normal 0 false false false IN X-NONE X-NONE


Armodafinil, the R enantiomer of modafinil, was approved in 2007 by the US Food and Drug Administration as a wake-promoting agent for excessive sleepiness treatment. Due to its abuse by students and athletes, there is a need of its quantification. Quantitative analysis by liquid chromatography-mass spectrometry, however, though very common and sensitive, frequently cannot be performed without isotopically labeled standards which usually have to be specially synthesized. Here we reported our investigation on the preparation of deuterated standard of armodafinil based on the simple and inexpensive hydrogen–deuterium exchange reaction at the carbon centers. The obtained results clearly indicate the possibility of introduction of three deuterons into the armodafinil molecule. The introduced deuterons do not undergo back exchange under neutral and acidic conditions. Moreover, the deuterated and non-deuterated armodafinil isotopologues revealed co-elution during the chromatographic analysis. The ability to control the degree of deuteration using different reaction conditions was determined. The proposed method of deuterated armodafinil standard preparation is rapid, cost-efficient and may be successfully used in its quantitative analysis by LC-MS.


Purpose: Scoliosis is a deformity of the spine, and as a measure of scoliosis severity, Cobb angle is fundamental to the diagnosis of deformities that require treatment. Conventional Cobb angle measurement and assessment is usually done manually, which is inherently time-consuming, and associated with high inter- and intra-observer variability. While there exist automatic scoliosis measurement methods, they suffer from insufficient accuracy. In this work, we propose a two-step segmentation-based deep learning architecture to automate Cobb angle measurement for scoliosis assessment using X-Ray images. Methods: The proposed architecture involves two steps. In the first step, we utilize a novel Augmented U-Net architecture to generate segmentations of vertebrae. The second step includes a non-learning-based pipeline to extract landmark coordinates from the segmented vertebrae and filter undesirable landmarks. Results: Our proposed Augmented U-Net architecture achieved a Symmetric Mean Absolute Percentage Error of 9.2%, with approximately 90% of estimations having less than 10 degrees difference compared with the AASCE-MICCAI challenge 2019 dataset ground truths. We further validated the model using an internal dataset and achieved almost the same level of performance. Conclusion: The proposed architecture is robust in providing automated spinal vertebrae segmentations and Cobb angle measurement, and is potentially generalizable to real-world clinical settings. Visual Abstract


In recent years, child neuropsychology has paid special attention to ontogenesis and trends in the development of practical functions during the preschool period, given their relationship to practical skills and children's readiness to learn. On the other hand, the dynamics of complex types of praxis is an indicator of the integration between the brain regions responsible for the perception, programming and recoding of motor patterns. The article presents a comparative analysis of data from a study of two types of praxis functions (dynamic praxis and spatial postural praxis) in children with typical development in the period 4–6 years. The specificity of the performance of neuropsychological tests is an indicator of the functioning and the degree of neuronal connectivity of the parietal and premotor regions of the left hemisphere. The data from the study show a similar trend in the dynamics of the studied functions and the influence on them of three independent factors: age, social conditions (type of settlement) and gender. Significant improvement in the performance of the tasks is observed in children at the age of 6, which is a reason to consider this age as critical for the maturation and neurophysiological connectivity of the structures of the parietal and premotor regions. The assessment of complex types of praxis in this period is an objective indicator of the neuropsychological development of children and has an indisputable prognostic effect for future learning disorders.


Part I. Law Itself, in General: 1. The essence of law 2. The different kinds of law 3. The effects of law Part II. The Parts of Law: 4. Of the eternal law 5. Of the natural law 6. Of human law 7. Of the divine law.


Following a strong demand for novel α-Al2O3 nano-materials with unique properties, both pure and doped nano-sheets, nano-needles, and nanosized equiaxed particles (reference) of 100% phase-pure α-Al2O3, were synthesized at 430–450 °C under 10.3 MPa pressure by the hydrothermal treatment of boehmite powder (γ-AlOOH) in the presence of α-Al2O3 seeds and 1–10% morphology modifiers. SiO2 and H3BO3 were used as morphology modifiers to produce phase pure α-Al2O3 nano-sheets and nano-needles, respectively, that exhibited strong crystallographic c- and a-faceting and BET surface areas up to 40 m2 g−1 stable above 1000 °C. A mesocrystal growth mechanism of the α-Al2O3 nano-particles was observed. Unprecedented flexibility to control the sizes and morphologies of α-Al2O3 enabled fabrication of 90% porous ceramics with unique pore geometries and pore volumes up to 1.5 cm3 g−1. These novel α-Al2O3 nano-materials can be useful in a variety of catalytic applications, nano-filtration, chemical-mechanical planarization, composites, etc.


Most hematological cancer-related relapses and deaths are caused by metastasis; thus, the importance of this process as a target of therapy should be considered. Hematological cancer is a type of cancer in which metabolism plays an essential role in progression. Therefore, we are required to block fundamental metastatic processes and develop specific preclinical and clinical strategies against those biomarkers involved in the metabolic regulation of hematological cancer cells, which do not rely on primary tumor responses. To understand progress in this field, we provide a summary of recent developments in the understanding of metabolism in hematological cancer and a general understanding of biomarkers currently used and under investigation for clinical and preclinical applications involving drug development. The signaling pathways involved in cancer cell metabolism are highlighted and shed light on how we could identify novel biomarkers involved in cancer development and treatment. This review provides new insights into biomolecular carriers that could be targeted as anticancer biomarkers.


Introduction Our study aimed to assess the efficacy of a local hemostatic, consisting of human thrombin and fibrinogen, which was applied on the aortotomy suture line. Material and methods The study involved 93 patients undergoing elective aortic valve replacement. Patients were randomized to two groups. Group 1 comprised 41 patients, in whom a hemostatic patch (Tachosil) was used additionally. Group 2 comprised 52 patients in whom Tachosil was not applied. Results The postoperative drainage after 48 h was significantly lower in the group of patients where the local hemostatic patch (Tachosil) was additionally used, compared to the control group (p = 0.0335). The prevalence of rethoracotomies was twice as high in the control group compared to the Tachosil group (5% vs. 10%), but the statistical analysis did not show a significant difference. As a consequence, both measurements of hemoglobin concentration revealed significantly higher hemoglobin in Tachosil-treated patients than the control group (p < 0.001, p = 0.0002). Red blood cell count (RBC) was also significantly higher in the Tachosil group. The difference in perioperative blood loss between the two groups resulted in a difference in postoperative acute renal injury or renal failure. The rate of infection within the early postoperative period was also comparable between the groups, although it was slightly higher in the Tachosil group (23% vs. 18%). The perioperative mortality was higher in group 2 but the difference was not statistically significant (3% in the Tachosil group vs. 5% in the control group). Conclusions Tachosil use reduced postoperative drainage considerably, which had an important influence on renal complications after aortic valve replacement.


The International Conference, "Building Bridges for Wellness through Counselling and Psychotherapy" was held at the Garden City Bangalore, India in the second week of January 2008. This conference was a collaborative initiative of Ontario Institute for Studies in Education–University of Toronto, Bangalore University-India and Sampurna Montfort College–Bangalore India. The conference aimed at sharing research and practice in counseling and psychotherapy including traditional healing practices within a context of multiculturalism and diversity. The preference was to integrate the religious, spiritual and transpersonal approaches in theory and practice for the counselors and psychotherapists worldwide.


This system provides online comprehensive solution to provide information regarding various Universities, their courses and admission procedures for admission seekers in courses or Programs. The system dedicates its resources to becoming the best university possible and giving students the resources both in Colleges and Courses to help them become competent professionals. Interested students can still take advantage of education programs. The system aims to maintain their proud academic and religious traditions while looking to the future and offering a range of online Course programs. Deciding that you want to go to college after high school is easy. Choosing the right college? Now that's tough. The college search process is tricky. Colleges, family members, friends and guidance counselors will all offer advice. But their influence may not be what's best for your college search. In this system, all the solutions has been included to help student related best college search and avoid some headaches.


This paper is focused on the study of the energy hole problem in the Progressive Multi-hop Rotational Clustered (PMRC)-structure, a highly scalable wireless sensor network (WSN) architecture. Based on an analysis on the traffic load distribution in PMRC-based WSNs, we propose a novel load-similar node distribution strategy combined with the Minimum Overlapping Layers (MOL) scheme to address the energy hole problem in PMRC-based WSNs. In this strategy, sensor nodes are deployed in the network area according to the load distribution. That is, more nodes shall be deployed in the range where the average load is higher, and then the loads among different areas in the sensor network tend to be balanced. Simulation results demonstrate that the load-similar node distribution strategy prolongs network lifetime and reduces the average packet latency in comparison with existing nonuniform node distribution and uniform node distribution strategies. Note that, besides the PMRC structure, the analysis model and the proposed load-similar node distribution strategy are also applicable to other multi-hop WSN structures.


We present a new approach for reconstructing a smooth surface from a set of scattered points in 3D space. Our algorithm first decomposes a given point set into a quadtree-like data structure known as a strip tree. The strip tree is used to fit a set of least squares quadratic surfaces to the data points. These quadratic surfaces are then degree-elevated to bi-cubic surfaces and blended together to form a set of B-spline surfaces that approximates the given point set.


Neural networks are vulnerable to adversarial examples, which poses a threat to their application in security sensitive systems. We propose high-level representation guided denoiser (HGD) as a defense for image classification. Standard denoiser suffers from the error amplification effect, in which small residual adversarial noise is progressively amplified and leads to wrong classifications. HGD overcomes this problem by using a loss function defined as the difference between the target model's outputs activated by the clean image and denoised image. Compared with ensemble adversarial training which is the state-of-the-art defending method on large images, HGD has three advantages. First, with HGD as a defense, the target model is more robust to either white-box or black-box adversarial attacks. Second, HGD can be trained on a small subset of the images and generalizes well to other images and unseen classes. Third, HGD can be transferred to defend models other than the one guiding it. In NIPS competition on defense against adversarial attacks, our HGD solution won the first place and outperformed other models by a large margin.1


With considerable NASA support, the scientific community has learned much in recent decades about the process of dendritic crystal formation, particularly as an example of steady-state pattern formation. Recently, efforts here and elsewhere have shifted towards the study of the timevarying aspects of the process. This paper will discuss the recent observations of the Transient Dendritic Solidification Experiment (TDSE). Data will be presented on the differences and similarities in the process by which two critical growth parameters, the growth rate and the tip radius of curvature, evolve as they approach steady state. This transient stage in the growth process is integral to many real-world industrial processes, and therefore a better understanding of it will serve as an important element of future industrial process models.


ABSTRACT This article compares four new automatic methods to discriminate between spruce, pine and birch, which are the dominating tree species in Norwegian forests. Airborne laser scanning and hyperspectral data were used. The laser scanning data was used to mask pixels with low or no vegetation in the hyperspectral data. A green–blue ratio was used to remove shadow areas from tree canopies, and the normalized difference vegetation index to remove dead vegetation and non-vegetation. The best method was hyperspectral pixel classification with 160 spectral channels in the visible and near-infrared spectrum, using a deep neural network. This method achieved 87% correct classification rate. Partial least squares regression for hyperspectral pixel classification achieved 78%. Deep neural network image classification using canopy height blended with three hyperspectral channels achieved 74%. A simple pixel classification method based on two spectral indices resulted in 67% correct classification. A possible future improvement is to find a better way to combine hyperspectral data with canopy height data in a deep neural network.


Aim: The current study undertook manipulative experiments to observe changes in snapping shrimp sound signals in relation to temperature and pH changes. Methodology: Sounds of intertidal snapping shrimp (Alpheus edwardsii) sequentially exposed to different temperature/pH treatments manipulation for a period of 2 week each, were recorded in the laboratory and analysed. The acoustic characteristics of snapping sound signal were examined to relate to the change in temperature, pH and combination of both parameters. Results: Our results showed that there was a significant reduction in the frequency of peak amplitude of snapping sound wave following a two week exposure to a combination of temperature and pH treatments. The frequency of snapping shrimp sound decreased by approximately 30% when exposed to a 2°C increase in temperature and a 0.7 unit decrease in pH, however, elevated temperature alone caused no significant effect on the peak frequency of snapping shrimp sound. Interpretation: The finding suggests that following the prediction values of temperature and pH changes due to climate change in the coming century may implicate the ambient noise at habitats where snapping shrimps dominate.


Sensor networks are a sensing, computing and communication infrastructure that are able to observe and respond to phenomena in the natural environment and in our physical and cyber infrastructure. The sensors themselves can range from small passive micro-sensors to larger scale, controllable weather-sensing platforms. In this work, we investigate how the sensor network performs in the case when the sink node moves. We consider as a metrics for evaluation goodput and Routing Efficiency (RE). We compare the simulation results when the sink node is mobile and stationary considering lattice topology using AODV protocol. The simulation results have shown that for the case of mobile sink, the goodput is better when the number of nodes is 16. However, when the number of nodes are 100 and 256, the goodput of mobile sink is worse than stationary sink when the values Tr is larger than 1pps. For both stationary and mobile sinks, the RE increases with the increase of number of sensor nodes, but the RE of mobile sink is better than the stationary sink.


Background: Lung infection is the world´s leading infectious cause of death. Bacterial parenchymal infection may cause lung cavities, which might impact treatment and prognosis. Aim : To evaluate predictive factors for the existence of cavities in bacterial lung infections and their outcomes. Methods: We included the last 27 patients admitted in a pulmonology ward due to cavitary bacterial lung infection, until December 2013. We also included the last 27 patients admitted due to bacterial parenchymal infection without cavities. Tuberculosis, HIV patients and nosocomial infections were excluded. Demographic, clinical and microbiological data, hospital stay length and mortality were compared between groups. Results: Patients with lung cavities were slightly younger (60 vs 65years, p=0.215). Men predominate in each group (p>0.05). Hospitalization in the previous 90 days was the only predictive factor for cavitary lung disease (OR=5.263, p=0.036). We identified bacteria in 30% of patients with lung cavities. The most frequent were P. aeruginosa (3), K. pneumonia (2) and E. coli (2). Only in 19% of patients without cavities was identified a bacteria. Hospital stay length was longer in patients with lung cavities (19 vs 12days, p=0.025). Mortality was also higher but not statistically different (15% vs 4%, p=0.159). Conclusions: Cavitary bacterial lung infections are associated to a longer hospital stay and to a higher mortality. In a pulmonology ward, the risk factors for cavitary infections described in literature (diabetes, age, neurologic or periodontal disease…) seem to be less relevant. Interestingly, a hospitalization in the previous 90 days was the only risk factor for a cavitary lung infection in these patients.


Montaigne's English Journey: Reading the Essays in Shakespeare's Day By William M. Hamlin Oxford: Oxford University Press, 2013 "[E]very abridgement of a good booke," Montaigne cautions, "is a foole abridged." Montaigne's warning was sound advice for early modern readers striving to reduce ponderous folios to neat epitomes for their commonplace books, and it remains good counsel for book reviewers--not least one undertaking a review of William M. Hamlin's Montaigne's English Journey: Reading the Essays in Shakespeare's Day, a tremendously rich and ambitious "good booke" that dedicates considerable attention to extractive reading and its limitations. Hamlin presents his project as "a descriptive account of English response to Montaigne during the early decades of his presence within the national vernacular and the English readerly imagination" (3). Naturally then, the focal point of Hamlin's book is the first complete translation of Montaigne's Essais into English: John Florio's The Essayes or, Morall, Politike and Militarie Discourses, of Lo[rd] Michaell de Montaigne, the version of Montaigne from which Shakespeare famously borrowed while composing The Tempest, and the volume Ben Jonson more than likely had in mind when a character in his Volpone names Montaigne among the authors from whom "English authors" habitually "steal" (3.4.87-90). While such renowned appropriators have their place in Hamlin's study, evidence left by humbler, and far more numerous, readers forms the backbone of Hamlin's "descriptive account." Hamlin is no stranger to things Montaignian--the French essayist also features prominently in his earlier monographs Tragedy and Scepticism in Shakespeare's England and The Image of America in Montaigne, Spenser, and Shakespeare--but here he couples that expertise with a methodological approach established by recent scholarship on early modern readership and manuscript culture. Following in particular the work of Heather Jackson (Marginalia: Readers Writing in Books), Heidi Brayman Hackel (Reading Material in Early Modern England), and William Sherman (Used Rooks: Marking Readers in Renaissance England), Hamlin offers a "large-scale case study of Florio's Montaigne during the first hundred years of its existence" with an eye toward the annotations made therein by early modern readers (2-3). To be precise, Hamlin has personally examined three-quarters of the surviving, publicly available copies of Florio's volume--263 of 353 institutional copies of the text's first three editions of 1603, 1613, and 1632--documenting in the process over 7000 annotations in seventeenth-century hands. He has also obtained digital images of relevant marginalia in any copies that he has not inspected in person, and he has compiled a working census of extant volumes (Appendix D). Moreover, Hamlin fleshes out his account of Montaigne's English reception by looking beyond Florio and his annotators. In addition to traditional close analysis of print appropriations by canonical authors, Hamlin considers letters and diary entries that discuss the Essayes, as well as commonplace books that excerpt from them. He even transcribes and edits three relevant manuscripts and includes them as appendices: a previously unknown English translation of large selections from eleven chapters of Book Two of the French Essais (Appendix A), an anonymous commonplace book dating from around 1650 that includes 198 extracts from Florio's Essayes (Appendix B), and "Montaigne's Moral Maxims," a collection of 297 aphorisms derived from Florio's text (Appendix C). Still, it is Florio's vibrant rendering that emerges as the key to the Montaigne's English reception in Hamlin's account. "Florio's Montaigne is not merely an English translation of a remarkable French book, but a reading of the Essays, indeed a reading in the service of a major act of rewriting" (32), Hamlin writes, and the claim is borne out by what follows. Hamlin demonstrates adroitly the mediating influence of Florio on the early modern English reception of Montaigne in his first chapter, "Florio's Theatrical Montaigne. …


The regenerative braking system (RBS) in electric vehicles (EVs) enhances its capability against internal combustion engines (ICE). Antilock braking system (ABS) is widely used in RBS because of its maneuverability and safety. One of the purposes of applying ABS is to avoid slippage. Slip on the braking process, especially hydraulic brakes, results in a difference in time to stop the wheels and the vehicle. It is avoided because it relies on friction between the tires and the road to stop transportation. Timing results showed that ABS with high frequency, above 30 Hz, tended to act like hydraulic brakes. Hydraulic brakes achieved the highest time difference, 8 seconds at 2250 rpm. It increased the distance of 350 m in slipping while the lowest time difference ABS 10 Hz owned, 0.1 seconds at the same rpm. Slips caused losses. These losses could be minimized with low-frequency ABS. It converted the friction between the wheels and the brakes into electrical energy instead of stopping the vehicle. As a result, the 10 Hz ABS had the highest potency stored despite the lowest performance.


Application of various mildly irritant substances to the posterosuperior and anteroinferior aspects of the external auditory canal of the rabbit, with intact ear drum and middle ear, produced cholesteatomas in the skin of the auditory canal, and the tympanic membrane particularly in the pars flaccida. At the anteroinferior insertion of the tympanic membrane, however, cholesteatoma growth could not be induced in these animal experiments. In severe diffuse otitis externa, secondary to the operative closure of the external auditory canal, cholesteatomas also preferably develop in the pars flaccida, the relatively thick, loose intermediate layer of connective tissue allows a rapid expansion of epithelial ridges thus favouring the formation of cholesteatoma in this region.


This paper introduces the fundamental principle and features of magneto-optical storage technology, and discuses the trend and a series of key techniques for increasing the data storage density of magneto-optical disk. The three ways including MO media, recording method and readout method for increasing the disk capacity have been discussed. Moreover, the importance with the exchange-coupled effect between the magnetic layers and recording domain morphology is emphasized.


Bandgap radiation in the presence of gaseous oxygen induces surface and selvedge photo-oxidation of amorphous GeS2. The phenomenon involves preferential oxidation of the Ge sites and may be understood in terms of the structural and electronic properties of GeS2. Such photo-oxidized films exhibit very different properties towards the subsequent deposition of Ag, as compared with untreated films. The inverse system (GeS2 deposition on Ag) exhibits markedly different interfacial properties, not previously recognized: this could have significant implications for the interpretation of bulk photodiffusion experiments.


Supervised deep neural networks (DNNs) have been extensively used in diverse tasks. Generally, training such DNNs with superior performance requires a large amount of labeled data. However, it is time-consuming and expensive to manually label the data, especially for tasks in remote sensing, e.g., change detection. The situation motivates us to resort to the existing related images with labels, from which the concept of change can be adapted to new images. However, the distributions of the related labeled images (source domain) and unlabeled new images (target domain) are similar but not identical. It impedes a change detection model learned from source domains being well applied to the target domain. In this paper, we propose a transferred deep learning-based change detection framework to solve this problem. It consists of pretraining and fine-tuning stages. In the pretraining process, we propose two tasks to be learned simultaneously, namely, change detection for the source domain with labels and reconstruction of the unlabeled target data. The auxiliary task aims to reconstruct the difference image (DI) for the target domain. DI is an effective feature, such that the auxiliary task is of much relevance to change detection. The lower layers are shared between these two tasks in the training process. It mitigates the distribution discrepancy between the source and target domains and makes the concept of change from the source domain adapt to the target domain. In addition, we evaluate three modes of the U-net architecture to merge the information for a pair of patches. To fine-tune the change detection network (CDN) for the target domain, two strategies are exploited to select the pixels that have a high possibility of being correctly classified by an unsupervised approach. The proposed method demonstrates an excellent capacity for adapting the concept of change from the source domain to the target domain. It outperforms the state-of-the-art change detection methods via experimental results on real remote sensing data sets.


Walter Hesselbach was born (20.1.1915) and grew up in Frankfurt/M. He was active in the socialdemocratic youth movement. After the Abitur (1933) he completed an apprenticeship as banker. Since 1940 he was soldier in the Wehrmacht and then became prisoner of war. Back in Frankfurt/M. in 1947 Hesselbach started his career as banker. Besides he was active in the Frankfurt SPD as a local politician. 1958 he got the mandate to unite the regional branches of the cooperative banks (Gemeinwirtschaftsbanken) owned by the trade unions. As head of the central executive board he formed the Bank fur Gemeinwirtschaft (BfG) into one of the most successful banks of the 1960ies and 1970ies. For Hesselbach, working for the BfG was not only an economic and social task; equally important he considered his political mission: He aimed at the reconciliation between Israel and Germany, he supported the Ostpolitik of Willy Brandt and he backed up the process of democratization in Spain and Portugal. When in 1977 he retired from the executive board the BfG was on the peak of it's success. Some years later, in 1982, the smash of the Neue Heimat marked the decline of the cooperative economy. This overshadowed the last years of Walter Hesselbach who died on the 5. November 1993.


This article discusses the ethical justification for, and reviews the American evidence on the effectiveness of, treatment for alcohol and heroin dependence that is provided under legal coercion to offenders whose alcohol and drug dependence has contributed to the commission of the offence with which they have been charged or convicted. The article focuses on legally coerced treatment for drink-driving offenders and heroin-dependent property offenders. It outlines the various arguments that have been made for providing such treatment under legal coercion, namely: the over-representation of alcohol and drug dependent persons in prison populations; the contributory causal role of alcohol and other drug problems in the offences that lead to their imprisonment; the high rates of relapse to drug use and criminal involvement after incarceration; the desirability of keeping injecting heroin users out of prisons as a way of reducing the transmission of infectious diseases such as HIV and hepatitis; and the putatively greater cost-effectiveness of treatment compared with incarceration. The ethical objections to legally coerced drug treatment are briefly discussed before the evidence on the effectiveness of legally coerced treatment for alcohol and other drug dependence is reviewed. The evidence, which is primarily from the USA, gives qualified support for some forms of legally coerced drug treatment, provided that these programs are well resourced, carefully implemented, and their performance is monitored to ensure that they provide a humane and effective alternative to imprisonment. Expectations about what these programs can achieve also need to be realistic.


A detailed electrochemical investigation of a series of iron complexes (biuret-modified tetraamido iron macrocycles FeIII -bTAML), including the first electrochemical generation of FeV (O), and demonstration of their efficacy as homogeneous catalysts for electrochemical water oxidation (WO) in aqueous medium are reported. Spectroelectrochemical and mass spectral studies indicated FeV (O) as the active oxidant, formed due to two redox transitions, which were assigned as FeIV (O)/FeIII (OH2 ) and FeV (O)/FeIV (O). The spectral properties of both of these high-valent iron oxo species perfectly match those of their chemically synthesised versions, which were thoroughly characterised by several spectroscopic techniques. The O-O bond-formation step occurs by nucleophilic attack of H2 O on FeV (O). A kinetic isotope effect of 3.2 indicates an atom-proton transfer (APT) mechanism. The reaction of chemically synthesised FeV (O) in CH3 CN and water was directly probed by electrochemistry and was found to be first-order in water. The pKa value of the buffer base plays a critical role in the rate-determining step by increasing the reaction rate several-fold. The electronic effect on redox potential, WO rates, and onset overpotential was studied by employing a series of iron complexes. The catalytic activity was enhanced by the presence of electron-withdrawing groups on the bTAML framework. Changing the substituents from OMe to NO2 resulted in an eightfold increase in reaction rate, while the overpotential increased threefold.


Industrial activities in India are associated with significant amounts of non – biodegradable solid waste and plastic waste. Plastic waste being prominent which is rarely recycled with as much as 40% left in landfill. Plastic waste is causing environmental pollution which is a major problem in the present era as the usage of plastic is growing day by day and it takes hundreds of years for plastic material to degrade. The plastic if burnt releases many toxic gases, which are very dangerous for health. So, there is an urgent need to recycle plastic waste so as to reduce the environmental impact. One possible way to minimize the plastic waste is to use plastic waste in concrete industry. Environmental concerns arising from the over dredging of sand have led to restriction on its extraction across India, a suitable environmental friendly alternative to sand must be found to match the huge demand in the concrete construction industry. To tackle both the issues plastic waste can be used in the concrete as the replacement of fine aggregate in known proportions. In this research work the fine aggregate has been replaced by two types of plastic waste, one is Low Density Polyethylene (LDPE) and second one is Polypropylene (PP) in varying proportions to find out the optimum content of plastic waste. The optimum content of plastic waste was determined by conducting tests on mechanical and durability properties. The mechanical test results shown that LDPE and PP plastic waste can be used in concrete mixtures up to 5% replacement level with fine aggregate. For this replacement level the durability property – Sulphate attack resistance was determined, results demonstrate the mass loss of specimens and compressive strength.


We demonstrate the generation of second-harmonic radiation in transmission through periodic and disordered arrays of sub-wavelength metallic apertures. For circular apertures in a square lattice, the second-harmonic signal peaks at incidence angles corresponding to enhanced transmission of the fundamental beam of 800 nm wavelength except at small incidence angles where the local symmetry minimizes the effective second-order nonlinear susceptibility of the apertures. Even though the linear transmission of the fundamental beam can be more than five times greater through the periodic array as compared to a disordered array, the strength of the second harmonic from the disordered array is greater at large incidence angles. By breaking the local symmetry through the use of apertures of non-centrosymmetric shape, the second-harmonic output occurs at fundamental transmission resonances at small incidence angles.


A simple analytical approach for stability assessment of underground storage caverns against ground uplift of overburden rock above the rock caverns for high pressurized fluid such as compressed air energy storage (CAES) and compressed natural gas (CNG) was developed. In the developed approach, we assumed that failure plane of the overburden is straight upward to ground surface, and factor of safety can be calculated from a limit equilibrium analysis in terms of this cylindrical shape failure model. The frictional resisting force on the failure plane was estimated by Hoek-Brown strength criterion which replaces with Mohr-Coulomb criterion such that both intact rock strength and rock mass conditions can be considered in the current approach. We carried out a parametric sensitivity analysis of strength parameters under various rock mass conditions and demonstrated that the factor of safety againt ground uplift was more sensitive to Mohr-Coulomb strength criterion rather than Hoek-Brown criterion.


License Plate recognition plays an important role on the traffic monitoring and parking management systems. In this paper, a fast and real time method has been proposed which has an appropriate application to find tilt and poor quality plates. In the proposed method, at the beginning, the image is converted into binary mode using adaptive threshold. Then, by using some edge detection and morphology operations, plate number location has been specified. Finally, if the plat has tilt, its tilt is removed away. This method has been tested on another paper data set that has different images of the background, considering distance, and angel of view so that the correct extraction rate of plate reached at 98.66%.


We study the physics of the solar corona as a whole, i.e. of the Sun as a Star, in order to understand its global features and to provide a template for stellar coronae. In this process we strive to understand the features of various structures which compose the solar corona. This process in not straightforward given the problems of observing the Sun as a whole: e.g., no recent X‐ray wide‐band, medium‐resolution, spectrum of the Sun is avaible, unlike stars and no X‐ray spectral monitoring of the Sun at various activity phases is available. The presentation will discuss our work in this field; we present the method we have devised, based on Yohkoh/SXT data, to derive the Differential Emission Measure vs. Temperature, and the X‐ray spectrum, of the solar corona, and the related main results. Finally we present some new results on flares and microflares and the implications on solar‐stellar coronal heating.


Colorectal cancer is the 4th most common cause of cancer related deaths worldwide and new possibilities in accurate diagnosis and targeted treatment are highly required. Mutations in adenomatous polyposis coli (APC) gene play a pivotal role in adenoma-carcinoma pathway of colorectal tumorigenesis. The quarter century from its´ first cloning, APC became one of the most frequently mutated, known driver genes in colorectal cancer. Intensive routine molecular testing of APC has brought the benefits for patients with family history of polyposis or colorectal cancer. Nevertheless, multiple mutational disease-causing mechanisms make the genetic testing still challenging. This minireview is focused on implementation of novel APC mutation screening diagnostic strategies for polyposis families according to the current findings. A further understanding and improved algorithms may help to increase the mutation detection rate. APC germline mutations achieve close to 100% penetrance, so more comprehensive approach followed by preventive and therapeutic strategies might reflect in decrease in burden of colorectal cancer.


A stellar dynamical model of the Milky Way Galaxy composed of an exponential disc, a cuspy bulge, and a NFW halo is studied. The model is subject to instability that form a bar with a pattern speed of 56 km/s/kpc and an exponential growth timescale of 250 Myr. The bar slows down after formation with a variable rate, which is largest just after formation, then decrease to 7 km/s/kpc per Gyr.
If the live halo of particles is substituted by a fixed external potential (rigid halo), the exponential growth timescale increases to 500 Myr, which would increase bar formation time from 3 to 6 Gyr in a disc represented by $10^{11}$ stars. Spectral analysis combined with time Fourier transformation shows the presence of bisymmetric `quasi-modes' with pattern speeds smaller than that of the bar. These modes disappear when the bar is strong enough, meanwhile a new nonlinear mode coupled to the bar appears with a pattern speed about 70 ... 75 % of the bar. This mode has a form of a trailing spiral extending to its corotation radius. Unlike the instability growth times, values of pattern speeds of bar- and quasi-modes in live and rigid halo models are similar.
A possibile reason for bar formation in a galaxy with cuspy bulge is due to the initial disc thickness, to which the pattern speed and orbit resonances are very sensitive. When a disc particle orbit reaches a height above the galactic plane comparable to radial distance, the motion is no longer periodic in radial direction. As a consequence, for radii of the order of the characteristic disc height, the radial frequency is ill defined and the inner Lindblad resonance (ILR) is smeared out. Accounting for the disc thickness in a toy model allows us to reproduce the bar mode in the rigid halo by a global mode analysis in the framework of linear perturbation theory. The dissipating role of the ILR is discussed.


Formaldehyde resins are used to improve the wet strength of paper. During the sheet-forming process of paper manufacture, formaldehyde fumes are liberated. Twenty-two male subjects having such exposures in a paper mill and 27 unexposed subjects were clinically evaluated to determine the effect of low level formaldehyde exposure in a tropical country. The workers were exposed to 0.03 mg formaldehyde/m3 air as an 8-h TWA. Formic acid excretion in urine was 37.2 +/- 18.9 and 20.3 +/- 4.2 ug/L among the exposed and the unexposed subjects, respectively. Significantly more respiratory problems (31.8%) were observed among the exposed subjects as compared to controls. Complaints pertaining to gastrointestinal, musculoskeletal and cardiovascular systems were also more frequent in exposed subjects. In spite of formaldehyde concentrations being well within the prescribed ACGIH limits of 1 ppm, the high rates of sickness emphasise the need for detailed studies on formaldehyde-exposed subjects in tropical countries.


Aim. To study the possibility of enhancing the antianginal effect of long-acting nitrates by their combination with trimetazidine in patients with stable angina. Material and methods. Patients with ischemic heart disease (IHD, stable angina; n=55) were included into the study. Patients were randomized to receive trimetazidine 35 mg 2 times a day (intervention group) or placebo (control group) in addition to standard therapy. A daily number of angina attacks, amount of short-acting nitroglycerin tablets consumed per week, exercise tolerance by the bicycle ergometry with the calculation of the threshold power and the work capacity were assessed at baseline and after 2 months of the drugs taking, as well as 2 months after the drugs withdrawal. Results. Significant reduction in nitroglycerin tablets consumption (1 month — by 61.8%, after 2 months — 72.5%, p<0.05) were found in the intervention group compared with the control group. Low intake of nitroglycerin compared with baseline (p<0.05) was maintained for 2 months after discontinuation of study drug. Significant increase in the threshold power (1 month — by 32.3%, after 2 months — 37.5%, p<0.05) was observed in the intervention group compared to baseline and with the control group. Conclusion. Trimetazidine in the treatment of stable angina has high clinical efficacy.


1. The intracellular distribution of alpha-D-mannosidase in homogenates of murine liver and spleen was investigated by differential and gradient density centrifugation. 2. In both tissues an enzyme with a neutral pH optimum was found in the cytosol together with an alpha-D-mannosidase with optimal activity between pH 5.5 and 6.0 which was also partially membrane-bound. 3. In liver the acidic alpha-D-mannosidase was obtained almost entirely in a particulate form distributed equally between a heterogeneous low density region and heavy density lysosomes. 4. The lysosomal form of the liver enzyme was purified to electrophoretic homogeneity and shown to be a glycoprotein composed of four identical subunits of molecular weight 65 kDa. 5. Antibody raised against the purified liver alpha-D-mannosidase immunoprecipitated a polypeptide from spleen which had the same molecular size. This acidic enzyme was the predominant type of alpha-D-mannosidase in spleen, but in contrast to liver, it was obtained mainly in a cytosoluble form, the remaining activity being present in the heterogeneous light density compartment. 6. Although both tissues contain the same molecular form of the acidic alpha-D-mannosidase, in murine spleen this enzyme does not appear to be associated with stable heavy density lysosomes.


Abstract This article seeks to understand the situation of political speech in Malaysia, the argument in favour of restrictions on political speech, and the problems that prevent political speech from being practised effectively. For example, two particularly sensitive issues—ethnic rivalry and religion—are considered taboo and discussion of these issues is severely restricted. Article 10 of the Malaysian Constitution, in reflecting the sensitiveness of these issues, specifies a list of restrictions, which limit the right of free speech on the grounds of guarding political stability and racial harmony. Furthermore, freedom of political speech and the political rights of individuals are secondary to the goals of national prosperity and national development, and the government is predisposed to impose some form of political discipline in order to serve the greater social good. However, the Malaysian government has taken a step further to control not only hate and racial speech, but also any political speech...


By integrating Mobile Edge Computing (MEC) into vehicular networks, vehicular edge computing extends computing capability to the vehicular network edge and hosts services in close proximity of connected vehicles. Parked Vehicles (PVs) occupy a large portion of the global vehicle and have idle states and resources. They collaborate with the MEC servers for cooperative task processing. This gives rise to a new computing paradigm, called by Collaborative Vehicular Edge Computing (CVEC). In CVEC, we introduce an offloading service provider that deploys an MEC server and schedules PVs on demand to handle offloading tasks. Efficient workload allocation and user-centric utility maximization are studied to optimize the network-wide task scheduling. In dynamic environment, offloading destination of each task is determined in a probabilistic manner. When necessary, the offloading service provider represents an offloading user to design a contract based incentive mechanism for the PVs. Based on contract theory and prospect theory, we model the offloading user's subjective evaluations on the utility in computation offloading, and derive an optimal contract to maximize the subjective utility under information asymmetry. Finally, numerical results are provided to demonstrate the effectiveness and efficiency of our scheme.


The higher-order genome organization and its variation in different cellular conditions remains poorly understood. Recent high-resolution genome-wide mapping of chromatin interactions using Hi-C has revealed that chromosomes in the human genome are spatially segregated into distinct subcompartments. However, due to the requirement on sequencing coverage of the Hi-C data to define subcompartments, to date subcompartment annotation is only available in the GM12878 cell line, making it impractical to compare Hi-C subcompartment patterns across multiple cell types. Here we develop a new computational approach, named Sniper, based on an autoencoder and multilayer perceptron classifier to infer subcompartments using typical Hi-C datasets with moderate coverage. We demonstrated that Sniper can accurately reveal subcompartments based on Hi-C datasets with moderate coverage and can significantly outperform an existing method that uses numerous epigenomic datasets as input features in GM12878. We applied Sniper to eight additional cell lines to identify the variation of Hi-C subcompartments across different cell types. Sniper revealed that chromosomal regions with conserved and more dynamic subcompartment annotations across cell types have different patterns of functional genomic features. This work demonstrates that Sniper is effective in identifying subcompartments without the need of high-coverage Hi-C data and has the potential to provide new insights into the spatial genome organization variation across different cell types.


Polysystem theory can explain some cases of literary translation. The article firstly gives a brief introduction of polysystem theory. According to the theory the writer analyzes the translation strategies of Zhu Qingying and Huang Yuanshen and its social causes in their different translated version of Jane Eyre.


Researchers are often evaluated by citation-based metrics. Such metrics can inform hiring, promotion, and funding decisions. Concerns have been expressed that popular citation-based metrics incentivize researchers to maximize the production of publications. Such incentives may not be optimal for scientific progress. Here we present a citation-based measure that rewards both productivity and taste: the researcher's ability to focus on impactful contributions. The presented measure, CAP, balances the impact of publications and their quantity, thus incentivizing researchers to consider whether a publication is a useful addition to the literature. CAP is simple, interpretable, and parameter-free. We analyze the characteristics of CAP for highly-cited researchers in biology, computer science, economics, and physics, using a corpus of millions of publications and hundreds of millions of citations with yearly temporal granularity. CAP produces qualitatively plausible outcomes and has a number of advantages over prior metrics. Results can be explored at this https URL


The precise variables of cell function are a result of the interaction between environ-mental factors such as nutrition and the genetic information present in the DNA. Thus, the modulation of gene expression by dietary components determines aspects of cell function, both normal and pathological: many nutritional and dietary effects on metabolism and tissue function will depend ultimately on the ability of specific nutrients to modulate the expression of genes and, thus, the extent of synthesis of specific proteins. Molecular biology techniques and gene cloning are important for nutritionists as they provide the tools and experimental approaches to study of the interaction between nutrition and gene expression.


Background
Recently, immunotherapy has changed the standard of treatment in non-small cell lung cancer (NSCLC). Outside clinical trials, data of real life is lacking. This is an observational study that represents the real world experience with nivolumab in pretreated NSCLC.

Methods
Eligibility criteria included, histologically confirmed NSCLC, stage IIIB and IV, evaluable disease and at least one prior therapy. Patients received nivolumab until progressive disease (PD) or unacceptable toxicity. The main aim of the study was to report the efficacy and safety profile of Nivolumab in pretreated patients with advanced NSCLC of our everyday clinical practice. The secondary aim was to perform subgroup analysis by clinical features.

Results
From August of 2015 to January of 2017, 188 patients were enrolled. The patients demographics were: median age 58 years, 144 male; 17 never smoker and 171 former/current smoker; 112 adenocarcinoma, 66 squamous-cell carcinoma and 10 not otherwise specified (NOS); 61 stage IIIB and 127 stage IV; 15 performance status (PS) 0, 154 PS 1 and 19 PS 2; 5 epidermal growth factor receptor (EGFR) and 1 anaplastic lymphoma kinase (ALK); 42 with central nervous system (CNS) metastases; and 71 received 2 or more prior therapy lines. Of the 188 patients enrolled, 25 (13.3%) were not evaluated, 3 (1.6%) had complete response (CR), 45 (23.9%) partial response (PR), 48 (25.5%) disease stabilization (DS) and 67 (35.6%) PD. The median of progression-free survival (PFS) was 4.83 months (95% CI, 3.6-5.9) and overall survival (OS) was 12.85 months (95% CI, 9.07-16.62). The subgroup analysis revealed statistical significance in OS for patients with CNS metastases 14.8 months (95% CI, 11.5-17.3) vs. 5.09 months (95% CI, 0.3-9.8) and also PS 0 [not reached (NR)] vs. PS 1 11.7 months vs. PS 2 3.4 months (95% CI, 2.3-4.4). The safety profile was in accordance with the literature data.

Conclusions
This study represents the real word experience with nivolumab and the results are consistent with previously reported in clinical trials. PS 2 and the presence of CNS metastases are associated with poor prognosis.


This report describes the work conducted by the Institute of Gas Technology, Dravo Corporation, and Williams Brothers Engineering Company during Phase II of the two-phase program. The objective of Phase I was to review the literature and identify needs in the areas of resources, harvesting, dewatering, beneficiation, gasification, and environmental studies. The results of Phase I have been previously reported (PB81-222275). The objectives of Phase II are to prepare updated peat resource maps and to conduct quantitative economic and environmental assessments of a few selected peat harvesting, dewatering, and beneficiation alternatives. In the task on peat resources, maps of fourteen states have been completed. A number of peat harvesting system designs have been ranked according to their technical merits and a preliminary economic assessment has been made of a wet harvesting method. A preliminary economic comparison of four peat dewatering systems has been made. A description of a beneficiation (wet-carbonization) process and a preliminary economic estimate for producing beneficiated peat is presented. Recent developments in both thermal and biological conversion of peat to SNG are described. The major air and water pollution emission rates from a peat gasification plant producing 250 billion Btu/day of SNG have been estimated. Detailed environmentalmore » scenarios have been prepared for three peat bogs typical of those in the Upper Midwest, Northeast, and Southeast United States. Preliminary cost estimates for harvested peatland reclamation options have been made.« less


Abstract : Study No. 1 with reference to our last report of 1978 immunization experiments with high doses of irradiation with Cobalt 60 are terminated and the study with its results are as follows. In a previous study a trial of inducing protection by Immunization of mice with low doses of cobalt 60 irradiated cercariae was carried out. The results were rather encouraging yet follow up of immunized animals failed to give satisfactory resistance to new infection.


From early antiquity through the end of the nineteenth century, the primary missions of Chinese imperial and private libraries were to collect and preserve books and documents. Except for a few isolated historical periods, these libraries rendered no service to the public. The Metropolitan University Library in Beijing, founded in 1898, was China's first modern academic library with a clear goal of serving a burgeoning program of public higher education. The tale of the founding of this library reveals an intriguing story of tension between the modern Western and traditional Chinese concepts of what a library should be. This article examines the changing patterns of Western influences and Chinese responses in the sociopolitical and cultural arenas in the nineteenth century and considers how, amidst this intense Western and Chinese engagement and confrontation, the debate on library reform emerged and eventually led to the birth of the modern Chinese academic library.


Mass manufacturing of optical fiber includes the process of very thin glass fiber drawing by heating and softening the high purity silica preform and applying the draw tension on the softened tip of preform neck-down profile in a draw furnace. In this computational study, this process is numerically modeled with simplified geometry of the draw furnace which is comprised of essential parts such as concentric graphite heater, muffle tube, and insulation surrounding the heater. The iterative computational scheme is employed between one-dimensional model of neck-down profile prediction and two-dimensional axisymmetric thermo-fluid CFD computation of radiative heating and working gas convection. The computational results show the experimentally observed neck-down profile in heated section of preform, while yielding the reasonable values of draw tension and heater wattage. Also, this study analyzes and discusses the effects of heating conditions such as heater length and temperature on several important aspects of glass fiber drawing process.


This study was performed to investigate the effects of isoprothiolane on cell growth and the production of interleukin (IL)-1 and IL-6 by bovine mammary epithelial cells in vitro. Isoprothiolane increased proliferation of mammary epithelial cells in a dose-dependent manner at the concentration of 0.05 to 5 microM when cultured either with or without serum-supplemented medium. In contrast, isoprothiolane (0.0005-5 microM) significantly inhibited the production of IL-1 and IL-6 by mammary epithelial cells. Moreover, the cytokines, IL-1alpha, IL-1beta, IL-6, and tumor necrosis factor (TNF)-alpha tended to inhibit the proliferation of mammary epithelial cells in a dose-dependent manner. These results indicated that isoprothiolane regulated mammary epithelial cell growth in vitro possibly by modulating the production of cytokines.


The process of above-threshold ionization of atoms is modeled by dividing it into two parts: an effective interaction that just lifts the electron into the continuum and a final state interaction between the electron and the laser field that is described by the Volkov solution. With an arbitrary unspecified effective interaction, the model readily exhibits peak switching and a reduced index of nonlinearity of the first peak. With the assumption of appropriate boundary conditions, peak suppression is obtained owing to the ponderomotive force. The consequences of modifying some of the assumptions that underlie the model are discussed.


A wavelength-multiplexed reflection-type photorefractive (PR) fiber hologram using a tunable visible-light laser diode is presented. We have shown that the wavelength-multiplexed PR fiber hologram offers a higher and more uniform wavelength selectivity than that of the transmission-type. Experimental demonstrations of wavelength-multiplexed reflection-type PR fiber hologram are provided, which are consistent with the theoretical analysis.<<ETX>>


Objective:To express two Livin isoforms (Livin α β genes) with transfection techniques in A549 cell line respectively in order to observe their effect on growth of cell line. Methods:Two eukaryotic expression vectors of Livin, pcDNA3.1-Livin α β, were transfected into A549 cell line by electroporation. Then G418-resistant clones were screened. RT-PCR, Northern blot and immunofluorescence cytochemistry were used to detect Livin α β expression level in the transfected cells. Finally, observation of cell morphology, growth curve assay and colony formation analysis were performed to explore the effect of Livin on growth of the cells. Results:Livin α β were expressed in transfected A549 cells, and induced a faster cell growth, shorter doubling time and stronger cell colony forming ability, yet had no morphology change.Conclusion:Both isoforms can accelerate the growth of A549 cells, indicating a close relationship between Livin expression and the genesis and development of lung cancer. The expression of Livin α β in A549 cells provides basis for further study of their different biological functions of anti-apoptosis and of their role in lung cancer cell resistance to radiotherapy and chemotherapy.


Probst, Glen, Spreitz, and Jung (2010) described an evaluation of the social validity of the parenting intervention Stepping Stones Triple P (SSTP). In this evaluation, 33 masters-level psychology students viewed one of the program resources and rated the strategies of quiet time and time out as lacking in both ethical acceptability and practical applicability. On the basis of this, the authors recommended revisions to the content of SSTP. The present paper provides additional information about SSTP to correct possible misconceptions, and provide further comments on Probst and colleagues' (2010) findings. SSTP has been demonstrated to be effective with a range of parents of children with diverse developmental disabilities and there is considerable support for the validity and effectiveness of the specific elements in question. Given this, it is argued that while there will inevitably be variations in how individuals accept program content, rather than altering program, it may be more appropriate to address those variables related to the acceptability of content. To this end, it is suggested that future research could usefully investigate influences on perceptions of content and, in particular, practical strategies to overcome barriers to the acceptance of socially valid and empirically supported methods. © 2010 Associazione Oasi Maria SS


8-Hydroxyquinoline derivatives are metal-binding compounds that have recently attracted interest as therapeutic agents for cancer therapy. In this scenario, we designed and synthesized three new glucoconjugates, 5,7-dichloro-8-quinolinyl-β-D-glucopyranoside, 5-chloro-8-quinolinyl-β-D-glucopyranoside and 2-methyl-8-quinolinyl-β-D-glucopyranoside and investigated their biological properties in comparison to the parent 8-hydroxyquinoline derivatives in the presence of Cu(2+). In vitro data show that 2 out of 3 glycosylated compounds possess a pharmacologically-relevant antiproliferative activity against tumor cells, similar to that of their parent compounds; this activity is associated with a relevant triggering of apoptosis. The pharmacological profile of the glucoconjugates depends on the cellular enzymatic β-glucosidase activity, as demonstrated by the inhibition of antiproliferative activity in the presence of the 2,5-dideoxy-2,5-imino-D-mannitol.


Case 1. A 38-year-old male was admitted with an 8-month history of progressive visual disturbance in his right eye. He had a past history of operations for paranasal sinusitis 24 years and 5 years prior to admission. Neurological examination revealed right anosmia, left hyposmia and vision in his right eye reducing to light perception. Case 2. A 61-year-old male was admitted with complaint of headache and a 2-month history of deteriorating vision in his right eye. On admission, vision in his right eye was found to be reduced to hand motions and associated with a concentric contraction of the visual field. Bilateral hyposmia and the right exophthalmos were also noticed. Plain x-ray films, tomography and especially CT scan were useful to demonstrate the definite inflammatory changes of the paranasal sinuses and the extension of the lesion beyond the confines of the sinuses. In both cases, external ethmoidectomy and sphenoidectomy with removal of the infected granulation tissue from the sinuses were performed, but neither mucocele nor pyocele was found. Vision improved postoperatively. Previous reports about ocular complications of infection in the paranasal sinuses without mucocele or pyocele are few. Early diagnosis of ocular complications of sinusitis is important. Once the diagnosis established, a timely surgical approach is essential to prevent visual loss.


1 The pharmacological characteristics of adrenoceptors mediating the positive inotropic action in the dog heart were assessed by the use of blood‐perfused papillary muscles and isolated strips of ventricular myocardium. 2 On the blood‐perfused papillary muscle driven at 2 Hz and in sinus node preparations, phenylephrine induced positive inotropic and chronotropic responses in the same dose range and was much less potent than isoprenaline. The dose‐response curve for the chronotropic action of phenylephrine was parallel to that of isoprenaline, whilst the dose‐response curve for the inotropic action of phenylephrine was less steep than that of isoprenaline. 3 The infusion of pindolol, a β‐adrenoceptor blocking agent, at a rate of 1 μg/min, shifted the isoprenaline dose‐response curves to the right, and to the same extent, in both papillary muscle and sinus node preparations. In contrast to isoprenaline, the antagonism of phenylephrine by pindolol was noncompetitive. Phentolamine did not affect the positive inotropic and chronotropic actions of phenylephrine. 4 On isolated ventricular strips α‐adrenoceptor blockade by 10−6m phentolamine did not affect dose‐response curves to phenylephrine or dopamine. Pindolol shifted the dopamine dose‐response curves to the right in a competitive manner and those of phenylephrine in a noncompetitive manner. 5 On ventricular strips from reserpine‐pretreated dogs phenylephrine and tyramine dose‐response curves were shifted markedly to the right and downwards. Desipramine (10−5m) which enhanced the action of noradrenaline considerably reduced the myocardial responses of phenylephrine. 6 Papaverine (10−5m) decreased the threshold concentration of phenylephrine required to stimulate the myocardium and shifted phenylephrine dose‐response curves to the left. 7 Raising the temperature from 32°C to 37°C shifted phenylephrine dose‐response curves to the right; when the temperature was raised from 37°C to 42°C the affinity of the drug was not changed. 8 Other α‐adrenoceptor stimulants, methoxamine and clonidine, decreased the active tension of ventricular strips. The responses to noradrenaline and adrenaline (in the presence of pindolol; 3 × 10−8m) were not affected by phentolamine (10−6m). 9 The results indicate that adrenoceptors mediating positive inotropic responses in the dog ventricle are of the /J‐type and that post‐synaptic α‐adrenoceptors are not involved. Phenylephrine acts mainly by releasing noradrenaline from adrenergic nerve endings and partly by a weak direct action on β‐adrenoceptors.


The RET (REarranged during Transfection) proto-oncogene encodes a tyrosine-kinase receptor specifically expressed in tissues originated from neuroectodermal tissues. Dominant-activating mutations in this RET proto-oncogene is often associated with Multiple Endocrine Neoplasia type 2A and 2B and Familial Medullary Thyroid Carcinoma syndromes, characterized by the occurrence of medullary thyroid carcinomas. Human medullary thyroid carcinoma cell line TT cell line harbours a MEN2A-type mutation, so this cell line could be a useful cell system to investigate the antitumor activity of new agents interfering with the function of RET oncogene in medually thyroid cancer. Recently, ellipticine and its derivatives were identified as excellent RET G-quadruplex stabilizing agents. Furthermore, these compounds also interfered with the transcriptional mechanism of the RET gene in TT cells, subsequently decreasing the endogenous RET protein expression. In present study, we demonstrated the specificity of NSC311152 by using papillary thyroid carcinoma (PTC) cells, the K1, which carry BRAF and PIK3CA mutations but lacks the dominant-activating mutations in this RET proto-oncogene. NSC311152 selectively suppresses cell proliferation by inhibiting the intracellular Raf/MEK/ERK and PI3K/Akt/mTOR signaling pathways in the TT cells. The systemic administration of NSC311152 in a mouse MTC xenograft model significantly inhibited the tumor growth through RET downregulation, whereas NSC31152 only showed a moderate antitumor activity against K1 xenograft tumors. Citation Format: Daekyu Sun, Vishnu Muthuraj Kumarasamy, Tariq Alqahtani. Selective antitumor activity of NSC311152 toward medullary thyroid cancer by downregulating the transcription of RET oncogene [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4783.


I. CHALLENGES AND TRENDS IN EARLY CHILDHOOD EDUCATION. 1. Challenges in Developing Programs for Young Children. II. LEADERSHIP AND THE ROLE OF THE DIRECTOR. 2. Understanding Leadership and the Use of Power. 3. Planning. 4. Decision-Making. 5. Creative and Analytical Problem-Solving. III. LEADERSHIP AND IMPLEMENTATION/HUMAN RESOURCES ISSUES. 6. Staff Selection, Development, and Evaluation. 7. Motivating Staff, Parents, and Children. 8. Team Building and Small Group Interaction. 9. Professionalism: More Than Meets the Eye. IV. LEADERSHIP AND HELPING CHILDREN IN THEIR ENVIRONMENT. 10. Parent Education and Parent Involvement. 11. Legal Issues in Early Childhood. 12. Medical Issues in Early Childhood. V. LEADERSHIP, OPERATIONAL ISSUES, AND EVALUATION. 13. Facilities, Equipment, Room Arrangement, and Scheduling. 14. Finances, Record-Keeping, Proposal Writing, and Evaluating. Appendix A: Home Learning Enablers. Appendix B: Parent Papers. Appendix C: Leadership Enablers. Appendix D: Motivator Activities. Appendix E: 14 Volunteer Program Papers (VPPs)-Classroom Volunteers. Appendix F: Early Childhood Websites. Index.


A flavonol glycoside (1) and a steroidal saponin (2), along with β-sitosterol and β-sitosterol-D-glucoside, were isolated from the roots of Smilax lanceaefolia Roxb. Mineral contents were determined using the atomic absorption spectrophotometer and the total antioxidant activity was determined using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging method.