Cataract is a very rarely encountered disease during childhood and in children with diabetes it has a prevalence of<1%. Risk factors: adolescence, history of long lasting hyperglycemia, diabetic ketoacidosis at onset, high level of HbA1c at onset and possibly genetic factors. Authors present the case of a 15 years boy, previously healthy, with history of type 2 diabetes, who presented acquired bilateral cataract immediately after diagnosis of diabetes. The adolescent presented clinical signs of diabetes, polyuria, polydipsia, severe weight loss, 4 weeks before the admission, and at admission he presented a severe form diabetic ketoacidosis. Biological tests at the onset of diabetes revealed: glycemia 900 mg/dl, HbA1c 16,4%, C Peptide 2.23 ng/ml, severe hydroelectrolytic modifications, autoantibodies were in normal range. Haematological, hepatic, renal tests and tyroid function were in normal range. Multiple dose insulin injection therapy with insulin analogues was administered from onset of diabetes. In evolution, the adolescent entered in remission period after 4 weeks from onset; the necessary of insulin in this period was<0,1 UI/kg, for 6 months. Currently, one year after the onset, weight (58 kg ), height (168 cm) and BMI (20) are normal, but the necessary of insulin increased again at 1.2 UI/kg/day. Ophthalmologic examination revealed a slightly positive evolution, posterior subcapsular densifications are delicate, he does not have vision disturbances. Paraclinical examinations reveal: HbA1c 5,9%, C Peptide 2,18 ng/ml, autoantibodies continue to be in normal range. At this adolescent it was difficult to establish the clinical form of diabetes mellitus. The presence of visual disturbances in children with diabetes mellitus in the first weeks or months after onset should raise suspicion of a possible cataract, so it is necessary to perform a complete ophthalmological examination. Therefore, early diagnosis is essential for sight preservation.


Computer assisted radionuclide angiography (CARNA) with 99mTc-DTPA was employed to study 143 patients with transient ischemic attacks (TIA) and 79 patients with prolonged reversible ischemic neurologic deficit (PRIND). The results of CARNA were compared with findings from radiographic angiography (RGA) in 173 patients and with findings in transmission computerized axial tomography (T-CAT) in 154 patients. In patients with TIA, CARNA showed a hemispherical perfusion deficit in 74.8%, and with PRIND 87.3%. This deficit, determined as the relative difference between the involved and the non-involved hemisphere, was significantly (p less than 0.0025) greater in PRIND (minus 23%) than in TIA (minus 17%). Sensitivity of CARNA was independent of the interval from ictus to examination for more than 4 months. RGA in TIA revealed true positives in 82.0%, in PRIND it was 89.5%. T-CAT was positive in TIA in only 16.8% but in PRIND it was 64.4%. Combined sensitivities in TIA (92.4%) and in PRIND (94.0%) were highest with the combination of CARNA and RGA. However, in PRIND the combination of non-invasive methods (CARNA and T-CAT) revealed 93.2% positive findings. Combinations of these evaluation methods may be used to detect cerebrovascular disease in patients with such dysfunction.


Aircraft noise metrics are used to assess airport and heliport noise impacts on host communities. Airports and heliports host communities need to be carried along to contribute to deliberations, understand proposals, and have their views heard on aircraft noise reduction strategies. People can feel disillusioned by noise metrics that are too complex and do not express what residents experience. Selecting the best noise metric is essential if all aviation stakeholders are to engage meaningfully on modalities for aircraft noise reduction. A single global noise metric that would capture all the factors influencing people's perception of aircraft noise and produce a definitive measure of annoyance is highly desirable, but such does not exist. Some of these noise metrics are simple but do not include subjective factors in their analysis; others that capture both the objective and subjective aspects of aircraft noise effects are complex and difficult to interpret. In selecting a noise metric to use for the measurement of aircraft noise, it is necessary to strike a balance between precision and simplicity. This paper examines the various noise metrics currently used to assess aircraft noise exposure globally and makes a case for equivalent continuous sound level(Leq) as the best based on the fact that it is easy to understand and communities can easily relate it to their experiences.


AIM
The aim of this study was to describe team leaders' experiences of facilitators and barriers of leadership in specialist palliative home care teams.

BACKGROUND
For effective teamwork in specialist palliative care, leadership is crucial; however, defining and agreeing on what leadership comprises may be challenging. In palliative care, teamwork is recognized as imperative for multiprofessional perspectives to meet dying patients' and families' needs.

METHODS
Qualitative interviews with 13 team leaders in specialist palliative home care were performed, using the Pettigrew and Whipp framework, and analysed with directed content analysis.

RESULTS
Team leaders' experiences of conditions influencing the organisation and delivery of specialist palliative home care is multifaceted and leaders seem conflicted in their approach to the multiple levels of leadership, vision and responsibilities.

CONCLUSION
Team leaders in specialist palliative home care described goals of care on differing levels and, for some, fiscal restraints and external pressures influenced their vision and leadership. Team leaders experienced challenges of leadership in relation to organisational issues, feeling burdened by responsibilities, budget restraints and team size.

IMPLICATIONS FOR NURSING MANAGEMENT
Team leadership is demanding and complex. In specialist palliative home care, affirming values and enabling vision during times of fiscal strain and external pressures, is challenging. For successful leadership that develops both individuals and the health care team, leaders are recommended to adapt the leadership style to the present situation surrounding the team.


The aim of this study was to analyze the scenario of medical residency programs (MRPs) in the north region of Brazil as well as the contextual determinants (socioeconomic, structural, and epidemiological) influencing the number of MRPs in this region. An ecological study was conducted using MRPs data from 2022. This study used multiple data sources. MRP indicators were described based on the Brazilian state and specialty. The dependent variable was the number of MRPs. The independent variables included sociodemographic, structural, and epidemiological factors. Poisson regression was performed to analyze the association between contextual variables and the number of MRPs. The results showed that only 3.6% of the municipalities had authorized MRPs. The idleness rate in the region was 46.0%, with family and community medicine as the specialties with the greatest idleness. The total density of authorized vacancies in the MRPs was 14.0 vacancies per 100,000 inhabitants. The models showed that with each increase of one unit of the vulnerability index (Socioeconomic Index in the Geographic Context for Health Studies—GeoSES), the number of MRPs increased, ranging from 8122 (p value < 0.001) to 11,138 (p value < 0.001). With each increase in undergraduate degrees in medicine, the number of MRPs increased by 0.945 (p value < 0.001). With each increase of 1 physician per 1000 population, the number of MRPs increased from 0.537 (p value < 0.001) to 0.845 (p value < 0.001). With each increase of one unit in general hospitals, specialized hospitals, teaching hospitals, and primary healthcare units, the number of MRPs increased by 0.176 (p value < 0.001), 0.168 (p value < 0.001), 0.022 (p value < 0.001) and 0.032 (p value < 0.001), respectively. Finally, with each increase of one death per 100,000 inhabitants, the overall mortality rate increased, ranging from 0.006 (p value < 0.001) to 0.022 (p value < 0.001). The study showed a low supply of MRPs in the northern region, a high rate of idleness, and important socioeconomic, structural, and epidemiological determinants of the number of MRPs.


Role of entrepreneurial innovations for human development is still invisible and subject to be investigated. This study uniquely unfolds the stratums of human development indicators caused by the activities of entrepreneurship. For this very purpose, the study utilizes the panel data of human development and entrepreneurship from 129 countries ranging for the years of 2016 to 2018. The human development has been measured through the human development index (HDI), and this data has been accessed from indicators of United nations development program (UNDP). The data of global entrepreneurial innovations (GEI) has been accessed from the global entrepreneurship and development index (GEDI). Both HDI and GEI comprised of composite indexes. GEI is the composite index with three sub-indices and 14 pillars. The three sub-indices are attitudes, abilities and aspiration. Out of 14 pillars opportunity perception, startup skills, risk acceptance, networking and cultural support are associated with attitudes. Opportunity startup, technology absorption, human capital and competition are associated with abilities while production innovation, process innovation, high growth, internationalization and risk capital are associated with aspiration. Although, the data of the HDI index was initially developed since 1990. However, due to non-availability of GEI data, only three years of panel data were included in the study. HDI comprised of three basic dimensions which include the knowledge, standard of living and healthy life. Based on the literature, the study hypothesized that global entrepreneurship positively affects human development worldwide. This proposed relationship was measured through generalized methods of moments through EViews. The data trend had been measured through a scatter diagram, before measuring the specific relationship among the major variables of the study. Through this test, normality of the data ad outliers was also checked. Data dispersion and linearity was checked through the test of standard residuals. After checking the appropriateness of data, parameters of the study were estimated. Results showed a strong and positive correlation between entrepreneurship and human development. By applying generalized methods of moments, the analysis revealed that entrepreneurial innovations could explain the 68 per cent variation in human development. So, it can be safely said that entrepreneurship is an important cause to enhance the capabilities of humans and can ultimately improve HDI worldwide. It is suggested that the nations who want to improve the skills, capabilities and living standards of humans in their respective regions should devise the strategies to promote the entrepreneurial activities.

Keywords
entrepreneurship, entrepreneurial ventures, human development indicators, global entrepreneurship development index, human development index, human capabilities, human skills, human capital.


Social media addiction problem emerges when the users cannot limit the use of social media networks and spend more time online. Today social media platforms have become work habits in many work areas as well media industry. So, it is important to determine the social media addiction tendency of university students who will work in the media after graduation. The aim of this research is to investigate social media addiction of the New Media and Journalism students, who were heavy users of new media tools, at Üsküdar University. The sample of the research consists of 85 students from New Media and Journalism Department. The research was conducted using a comparative survey model, with the data collected from Social Media Addiction Scale developed by Tutgun-Ünal and Deniz (2015); and social media addiction of students were examined in terms of various demographic variables. In the research, social media addiction of the students was found to be low. When the sub-scales were examined, occupation and mood modification levels of social media addiction of students were found to be moderate. The findings of the research revealed that (a) Social media addiction increases as the daily time spent increases, (b) Students sharing photos in social media by applying filter/makeup were found to be more addicted regarding the mood modification aspect, (c) Students use social media when they wake up in the morning, during the day, and before bed, (d) New Media and Journalism students' Instagram use is high, followed by students using Twitter the most.


Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel zoonotic coronavirus that was identified in 2012. MERS-CoV infection in humans can result in an acute, severe respiratory disease and in some cases multi-organ failure; the global mortality rate is approximately 35 %. The MERS-CoV spike (S) protein is a major target for neutralizing antibodies in infected patients. The MERS-CoV microneutralization test (MNt) is the gold standard method for demonstrating prior infection. However, this method requires the use of live MERS-CoV in biosafety level 3 (BSL-3) containment. The present work describes the generation and validation of S protein-bearing vesicular stomatitis virus (VSV) pseudotype particles (VSV-MERS-CoV-S) in which the VSV glycoprotein G gene has been replaced by the luciferase reporter gene, followed by the establishment of a pseudoparticle-based neutralization test to detect MERS-CoV neutralizing antibodies under BSL-2 conditions. Using a panel of human sera from confirmed MERS-CoV patients, the VSV-MERS-CoV particle neutralization assay produced results that were highly comparable to those of the microneutralization test using live MERS-CoV. The results suggest that the VSV-MERS-CoV-S pseudotype neutralization assay offers a highly specific, sensitive and safer alternative method to detect MERS-CoV neutralizing antibodies in human sera.


The two one-sided t-tests (TOST) procedure has been used to evaluate average bioequivalence (BE). As a regulatory standard, it is crucial that TOST distinguish BE from not-BE (NBE) when BE data are not lognormal. TOST was compared with a Bayesian procedure (BEST by Kruschke) in simulated datasets of test/reference ratios (T/R) which were BE and NBE, wherein (1) log(T/R) or T-R were normally distributed, (2) sample sizes ranged 10–50, and (3) extreme log(T/R) or T-R values were randomly included in datasets. The 90% "credible interval" (CrI) from BEST is a Bayesian alternative of the 90% confidence interval (CI) of TOST and it can be derived from a posterior distribution that is more reflective of the observed mean log(T/R) distribution that often deviates from normality. In the absence of extreme T/R values, both methods agreed BE when observed T/R were lognormal. BEST more accurately concluded BE or NBE, while requiring fewer subjects, when observed log(T/R) or T-R were normal in the presence of extreme values. Overall, TOST and BEST perform comparably on lognormal T/R, while BEST is more accurate, requiring fewer subjects when datasets are normal for T-R or contain extreme values. Of note, the normally distributed datasets only rarely contain extreme values. Our results imply that when BEST and TOST yield different BE assessment results from bioequivalent products, TOST may disadvantage applicants when T/R are not lognormal and/or include extreme T/R values. Application of BEST can address the situation when T/R are not lognormal or include extreme data values. Application of BEST to BE data can be considered a useful alternative to TOST for evaluation of BE and for efficient development of BE formulations.


Abstract The method of partially invariant solutions of PDE systems was introduced by Ovsiannikov as a generalization of the classical similarity analysis. It offers a possibility to calculate exact solutions possessing a higher degree of freedom than similarity solutions. Ovsiannikov's algorithm, however, is somewhat hard to apply because one has to deal with three equation systems derived from the original PDE system. By means of the two-dimensional Euler equations, we show how the algorithm can be essentially simplified if classical similarity solutions are already known. Further, we prove a necessary criterion for the simplified algorithm to be senseful.


Aim of the study: To analyze the changes in DNA content, the percentage of apoptosis and the nuclear mitotic frequency of myocytes in transplanted human hearts. Methods: Twenty-three transplanted hearts were obtained from 22 patients. The mean interval between transplantation and death was 649 days (ranging from 13 to 2558 days). Ten control hearts were selected from individuals whose death was not due to primary heart disease. Tissue samples were obtained from the mid section of the lateral wall of left and right ventricles. DNA content was evaluated on isolated myocardial cells using image cytometry. In situ detection of apoptosis was performed by the terminal deoxynucleotidyl transferase-mediated digoxigenin-dUTP nick-end labeling (TUNEL) technique. Mitotic figures were examined by staining the nuclear DNA with YOYO-1 iodide. Myocytes were distinguished from stromal cells by using antibodies reacting with a-sarcomeric actin. Results: Comparing with control hearts, the myocytic changes after cardiac transplantation are characterized by: 1) a decrease in mononucleated myocytes and an increase in binucleated and multinucleated myocytes; 2) a decrease in diploid myocytic nuclei and a distinct augmentation of intermediate ploidies; 3) an increase in myocytic nuclei in DNA ploidies higher than 4c; 4) a marked augmentation of percentage of apoptotic myocytes and 5) an increased frequency of nuclear mitosis of myocytes; this fact appears as a declining phenomenon after six months of cardiac transplantation. Conclusion: After cardiac transplantation the DNA content of myocytes shows two completely different aspects: 1) a distinct increase in subdiploidy and intermediate ploidies related to myocyte injury induced by apoptosis and necrosis; 2) an increase in multinucleation, polyploidization and mitotic proliferation. Both myocyte growth and myocyte injury alter the function of the allograft and contribute to adaptation or failure of the graft. Furthermore, a relevant difference of age between the recipient and the donor may lead to a more marked myocyte damage and a lower myocyte growth. This tendency provides an evidence that age matching could be an important aspect in selecting the donor for the recipient.


Socio-political aspect is one of the dimensions of human life. An important issue is the view of Islam towards the formation of government at the age of occultation. Concerning the certain traditions, any kind of uprising and revolution before the emergence of Hazrat Qaem (a.j.) will be unlawful and add, "Any flag which raised before the emergence of the Imam of the Age (a.j.), its leader will be Taqut." The present study aimed at criticizing the narrative bases of the revolution opponents and the formation of government from the viewpoints of documents and contexts. Based on the results, only one, and with tolerance, two traditions ban the uprising and describe the rebels as Taqut, legends from Malek Jahani, and Abi basir. Both narratives have some flaws from the viewpoint of documents and rejected contextually. They are not in agreement with the Quran, necessities of religion, the Shia idea of fighting against oppression, and the practical life of the religious leaders. These traditions, in the event of the correctness of their reference to infallible Imams (a.s.), provide for uprisings whose leaders instead of Sovereignty of Allah and Ahl al- Bayt [The household of the Prophet (P.B.U.H)] introduce themselves as the promised Mahdi (a.j.).


ABSTRACT Transcriptional transactivation of the human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR) promoter element by the essential viral Tat protein requires recruitment of positive transcription elongation factor b (P-TEFb) to the viral TAR RNA target. The recruitment of P-TEFb, which has been proposed to be necessary and sufficient for activation of viral gene expression, is mediated by the highly cooperative interaction of Tat and cyclin T1, an essential component of P-TEFb, with the HIV-1 TAR element. Species, such as rodents, that encode cyclin T1 variants that are unable to support TAR binding by the Tat-cyclin T1 heterodimer are also unable to support HIV-1 Tat function. In contrast, we here demonstrate that the bovine immunodeficiency virus (BIV) Tat protein is fully able to bind to BIV TAR both in vivo and in vitro in the absence of any cellular cofactor. Nevertheless, BIV Tat can specifically recruit cyclin T1 to the BIV TAR element, and this recruitment is as essential for BIV Tat function as it is for HIV-1 Tat activity. However, because the cyclin T1 protein does not contribute to TAR binding, BIV Tat is able to function effectively in cells from several species that do not support HIV-1 Tat function. Thus, BIV Tat, while apparently dependent on the same cellular cofactor as the Tat proteins encoded by other lentiviruses, is nevertheless unique in terms of the mechanism used to recruit the BIV Tat-cyclin T1 complex to the viral LTR promoter.


A comprehensive totally aqueous phase synthesis of nickel-nitrilotriacetate (Ni-NTA) modified superparamagnetic Fe3O4 nanoparticles is presented. The Fe3O4-NTA–Ni nanoparticles are able to perform efficient and specific purification of 6-His tagged proteins from crude cell lysates, as evidenced by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) and Western blot analysis. The average binding capacity, as demonstrated by streptopain (MW 42 kDa), is 0.23 mg/mg (protein/Fe3O4-NTA–Ni). Considering the high affinity and specificity of the binding between hexahistidine motif and Ni-NTA, Ni-NTA modified nanoparticles could act as a module to carry 6-His tagged proteins on the particle surface with molecular orientation control, since only the 6-His domain could be attached. These modularly designed functional nanoparticles enhance cancer cell targeting, as supported by the in vitro receptor mediated targeting assay using RGD-4C-6-His fusion peptide. The nanoparticles show no significant hemolysis for human blood and could be investigated further for their in vivo functional imaging applications.


This study presents an empirical analysis related to the following research question: What is the Portuguese chartered accountants' perception of the role of the autonomous taxation of expenses (ATE) in small and medium firms' level of tax compliance, and especially when this perception is mediated by factors such as the size and the economic activity of firms?
The authors tested to determine if there are differences in the perceptions of accountants, and results show that the respondents' application of ATE to micro and small companies has a positive impact on their perceptions of tax compliance. The same is not valid for medium-sized companies for which there is no significant effect on the perceptions of the role of ATE on small and medium enterprises (SME) tax compliance.
Tax compliance, autonomous taxation of expenses, chartered accountants, small firms, Portugal.


Currently, the best option for patients with hepatitis delta is interferon alpha therapy for at least one year. To evaluate the effect of the combination lamivudine–high‐dose interferon alpha therapy, we first treated eight patients with chronic hepatitis delta infection with lamivudine for at least 24 weeks; then lamivudine was combined with a high dose of interferon alpha followed by a regular dose (9 MU tiw). Follow‐up was 12 weeks. Virological, biochemical and histological features were evaluated for response to therapy. At baseline, all patients were HBsAg positive in serum and HDV RNA‐(PCR)positive in plasma; HBV DNA was undetectable with the Digene Hybrid Capture assay (limit of detection 1.5 × 106 geq ml–1) in all cases. Transaminases were elevated in all patients; median ALT 68 (range 48–143) IU l–1. Seven of eight patients completed the course; one patient with a pre‐existing sickle cell trait was withdrawn from the trial due to the development of a nephrotic syndrome. The HBsAg‐concentration in serum decreased in two out of seven patients (29%). However, there was no significant decrease in the HBsAg‐concentration in serum during treatment (median 3654 PEU l–1 (range 548–7684) to 5300 PEU l–1 (range 168–19639)). The drop of HDV RNA in plasma from baseline during treatment was not significant. Decrease of HDV RNA was observed in three out of seven patients (43%) (median 105 geq ml–1; range 103–106 to median 103 geq ml–1; range 102–107). Serum ALT did not change as reflected by a median of 68 IU l–1 (range 48–143) at start of therapy to 63 IU l–1 (range 20–171) at the end of therapy. At the end of treatment transaminases had normalised in one patient and decreased in three other patients (improvement in 57%). However, three of these four patients showed a rebound after withdrawal of therapy. The Histology Activity Index (HAI) indicated a drop from a median score of 7 (range 5–9) at baseline to 5 (range 3–8) at the end of treatment, but an increase in fibrosis from a median grade of 2 (range 1–3) at baseline to 3 (range 1–4) at the end of treatment was observed. In conclusion, this study does not yield support for the combination of an HBVsuppressor and 16 weeks of high‐dose interferon for therapy aimed at eradicating the hepatitis delta virus.


The idea that the concepts of aromaticity and antiaromaticity apply to molecules in other than their electronic ground states can be traced back to Baird who argued that the well-known 4n+2 and 4n rules for ground-state aromaticity in cyclic conjugated hydrocarbons are reversed in their lowest triplet states: rings with 4n π electrons become aromatic while 4n+2 systems should be regarded as antiaromatic. We show that Baird's 'triplet' aromaticity and antiaromaticity represent particular cases of broader concepts of excited state aromaticity and antiaromaticity. Magnetic criteria including nucleus-independent chemical shifts (NICS), proton shieldings and magnetic susceptibilities calculated using complete-active-space selfconsistent field (CASSCF) wavefunctions constructed from gauge-including atomic orbitals (GIAOs) strongly suggest that, in contrast to the well-known aromaticity of the S0 state of benzene, the T1 and S1 states of this molecule are antiaromatic, whereas in the two most popular examples of antiaromatic cycles, square cyclobutadiene and D8h cyclooctatetraene, the T1 and S1 states are aromatic.These findings can
be rationalized using valence-bond models in which aromaticity and antiaromaticity are associated with resonance and antiresonance


ECAP (Equal Channel Angular Pressing) is a technique used to enhance the strength of material by grain refinement. In this research, an aerospace grade aluminum alloy-6061 is investigated. The specimens were pressed through ECAP die channels, intersecting each other at an angle of 90oC where a shear plane of 45oC was developed, that results grains refinement. Fatigue strengths and CGR (Crack Growth Rate) for the stress ratio R 0.7 and 0.1 are found and compared with the as-received material.It was observed that the CGR is slower at stress ratio R=0.1, as compared to stress ration R=0.7. An electric furnace was embedded with ECAP die to regulate the material flow through this die. The temperature of the die was maintained at 450oC during ECAP pressing and the specimens were also preheated at this temperature using another furnace. The ECAP die consists of two channels intersecting at 90o provided with safe inner and outer corner radius to avoid scaling.The microstructural observations revealed that the deformation was perfectly plastic. The ECAPed and as-received materials were also characterized by tensile tests, micro-hardness tests, and 3-point bend fatigue tests.


Studies of cultivatable human immunodeficiency virus type 1 (HIV-1) from plasma samples from infected patients have shown a correspondence between increasing viral burden and disease progression, but these measurements are selective and thus nonrepresentative of the in vivo viral load. Quantitation of proviral DNA sequences by the polymerase chain reaction in purified CD4+ T cells has shown a similar relationship but does not provide a measure of viral gene expression. We have studied viral DNA, genomic RNA, and spliced mRNA expression of HIV-1 in infected patients with a quantitative polymerase chain reaction assay. Viral RNA expression is detected in all stages of infection. These data show that the natural history of HIV infection is associated with a shift in the balance of viral expression favoring the production of genomic RNA without a preceding period of true viral latency.


TRPV1 mediates pain occurring during sickling episodes in sickle cell disease (SCD). We examined if hemin, a porphyrin released during intravascular hemolysis modulates TRPV1. Calcium imaging and patch clamp were employed to examine effects of hemin on mouse dorsal root ganglion (DRG) neurons and HEK293t cells expressing TRPV1 and TRPA1. Hemin induced a concentration-dependent calcium influx in DRG neurons which was abolished by the unspecific TRP-channel inhibitor ruthenium red. The selective TRPV1-inhibitor BCTC or genetic deletion of TRPV1 only marginally impaired hemin-induced calcium influx in DRG neurons. While hTRPV1 expressed in HEK293 cells mediated a hemin-induced calcium influx which was blocked by BCTC, patch clamp recordings only showed potentiated proton- and heat-evoked currents. This effect was abolished by the PKC-inhibitor chelerythrine chloride and in protein kinase C (PKC)-insensitive TRPV1-mutants. Hemin-induced calcium influx through TRPV1 was only partly PKC-sensitive, but it was abolished by the reducing agent dithiothreitol (DTT). In contrast, hemin-induced potentiation of inward currents was not reduced by DTT. Hemin also induced a redox-dependent calcium influx, but not inward currents on hTRPA1. Our data suggest that hemin induces a PKC-mediated sensitization of TRPV1. However, it also acts as a photosensitizer when exposed to UVA-light used for calcium imaging. The resulting activation of redox-sensitive ion channels such as TRPV1 and TRPA1 may be an in vitro artifact with limited physiological relevance.


Current and pending regulations concerning hazardous substances can create new and complex challenges for the hospital safety manager. Compliance can be made much easier if you have the right computer database. Here is a review of one such database that is now in existence at a Philadelphia hospital.


The combination of ultrahigh-molecular-weight polyethylene (UHMWPE) pads and zirconia joints has been used extensively in all artificial knee joints. The wear of UHMWPE is the leading cause of artificial joint failure. However, it is unlikely to detect UHMWPE damage until the patient feels pain. Therefore, developing a sensor to detect the wear of UHMWPE outside the human body is crucial. In this study, the surface of UHMWPE and zirconia was treated with low-temperature atmospheric plasma to increase the surface energy so that the lubricating fluid can be effectively adsorbed on the surface of the material. Furthermore, adding the appropriate proportion of hydroxypropyl methylcellulose with collagen produces good self-assembly behavior, which can reduce the UHMWPE wear and coefficient of friction (COF) by 50%. Therefore, the wear consumption of UHMWPE can be observed simply by sensing the changes in COF, which can be used as a life sensor for joint damage. At a distance of 9500 m continuous use, the COF increases by 17%, which means that the use of UHMWPE can be predicted by detecting the changes in COF. Finally, we proposed that the artificial knee joint's service life can be detected by monitoring the variation in COF.


Choosing the best out of an increasing number of options requires reliable and accurate information. As our time and resources are limited, we commonly use the experience of others in order to take decisions. Reputation mechanisms aggregate in a formal way the feedback collected from peers and compute the ``reputation'' of products, services, or providers. They enjoy huge success and are believed to be the key of the agent mediated commerce of tomorrow. Obtaining honest feedback from self-interested agents is not a trivial problem. Mechanisms based on side-payments can be conceived such that honest reporting becomes rational (i.e. Nash equilibrium). Unfortunately, for every incentive-compatible Nash equilibrium there seems to also be a dishonest Nash equilibrium strategy that sometimes is more attractive. In this paper we analyze two incentive-compatible reputation mechanisms and investigate how undesired equilibrium points can be eliminated by using trusted (i.e. true) reports.


The metal-insulator-semiconductor (MIS) and high electron mobility transistor (HEMT) implementations of the spin field effect transistor (SpinFET) proposed by Datta and Das are considered. In both configurations, the SpinFET's switching voltage (for switching on or off) and power dissipation are found to be larger than those of the traditional MISFET or HEMT if the channel length is les 90 nm. This is a consequence of the fact that spin orbit interaction strengths in semiconductors are too weak to impart any significant advantage to the SpinFET. The issue of non-ideal spin injection and detection at the source and drain contacts is also considered. The SpinFET's on-to-off conductance ratio rapidly degrades with decreasing spin injection/detection efficiency, dropping from infinity (for a one-dimensional channel) to as low as ~9.5, if the spin injection/detection efficiency drops from 100% to 90%. The transconductance has a quadratic dependence on the spin injection efficiency. These analyses are valid at arbitrary temperatures.


A recognised challenge for climate litigation is the fundamental incompatibility between the climate change problem and legal systems' ability to hold critical players accountable. Locus standi and causation are critical stumbling blocks in the quest for climate justice. In Kenya, the requirements for locus standi and causation in public interest environmental litigation have been evolving. This article explores this evolution, showing three ways in which this creates opportunities for climate litigation. Firstly, there is no need to show particularised injury, which allows any person to sue for climate-related actions or inactions. Secondly, liability routes have been created that allow litigants to avoid the restrictive causation requirements, so that the plaintiff would not have to show any injury, let alone link harms to emissions from specific entities or to inaction. Thirdly, the courts take a precautionary approach which then shifts the burden of proof to the defendants, who are required to show that their activities or inaction do not pose a threat of serious or irreversible damage. These recent developments provide the needed legal opportunities for climate litigation and could make Kenya a potential hotspot for future climate change cases.


Turkish Society of Nephrology registry collects data on hemodialysis, peritoneal dialysis and transplantation on annual basis. Registry reports are printed every year as a booklet and this is the 20 th year of registry reports. The registry is in close collaboration with international registries. In this paper data from the 2009 registry report are summarized, additionally yearly trends in the management of end stage renal disease are also provided The number of patients on renal replacement therapy is rapidly increasing, at the end of 2009, 59443 patients were on renal replacement therapy. The prevalence and incidence of end stage renal disease was 819 and 197 per million population respectively. Diabetes was the most important cause of end stage renal disease. Hemodialysis (78.5%) was the most common type of treatment modality, followed by transplantation (12.4%) and peritoneal dialysis (9.1%) End stage renal disease is a very important and growing health problem for our country. Renal registry is a leading tool for providing current and sound data on this public health problem.


This research paper is going to elaborate Middlemarch, one of the greatest works of George Elliot (her real name was Marie Ann Evans). It is one of the major pieces of the thesaurus of British Victorian period. The novel is subtitled as 'A study of Provincial Life' which is set in the imaginary town of Middlemarch which is thought to be at the territory of today's city of Coventry, a little town not far from Oxford. The story takes place between the periods of 1930-1932.Elliot presents the stories of a number of denizens of a small English town on the eve of the Representation of the People Act Bill. This Reform Bill endorsed major changes in the parliament where the number of commoners increased. Middlemarch is her seventh novel, started to be written in 1869.The interruption of her writing was caused by the illness of Thornton Lewes, the son of her partner George Henry Lewes. Elliot's resumed works; fusing together several stories into coherent whole during 1871-1872, appeared in serial form. The Volume I Edition was published in 1874 and attracted a large publicity. The novel is composed of eight books; it contains also a prelude and a postscript or a finale describing the post-novel fates of the main characters. The narrator is an omniscient third-person singular that narrates the life of ordinary people isn't granting the echelon of heroic princes and kings. As a realistic novel Middlemarch contains multiple and different characteristics of realism such as; a slow-moving plot, emphasis on morality, casualty, foreshadowing of everyday events, emphasis on psychological optimistic tone, too much details, events are usually plausible. The research methods that have been helpful while conducting this research paper are; narrative and descriptive methods.


This study was undertaken to observe the effects of organic or inorganic calcium antagonists and to investigate the involvement of cyclic nucleotides in regulating the vascular tone in the chorionic artery from normal or preeclamptic placenta. KCI and prostaglandin (PG) F2 alpha produced marked and constant contractions in chorionic arterial preparations of both normal and preeclamptic placentas. Nifedipine (NIF), verapamil (VER) and diltiazem (DIL) reduced the tension that had been produced by KCI and PGF2 alpha in a concentration-dependent fashion in both preparations, and the potency order of the three agents was NIF > VER > DIL. In preeclamptic arteries, however, the magnitudes of vasodilatation induced by NIF and DIL were much smaller than those in normal chorionic arteries. Mg2+ and Cd2+ also relaxed the tension induced by KCI and PGF2 alpha. In preeclamptic chorionic artery, the vasodilatation induced by Mg2+ was significantly potentiated, while that by Cd2+ was not. Removing endothelium did not alter cyclic GMP content in both preparations. In both preparations contracted by PGF2 alpha, nitroprusside markedly increased cyclic GMP content, but neither cyclic GMP nor cyclic AMP content was affected by acetylcholine, NIF, isopro-terenol, or Mg2+. The above results suggest that neither cyclic AMP nor cyclic GMP is involved in regulating the vascular tone of chorionic artery and that sensitivity of the artery in preeclampsia to the inhibitory action of calcium antagonist might be different from that in normal placenta.


ABSTRACT Intermolecular recombination between the genomes of closely related RNA viruses can result in the emergence of novel strains with altered pathogenic potential and antigenicity. Although recombination between flavivirus genomes has never been demonstrated experimentally, the potential risk of generating undesirable recombinants has nevertheless been a matter of concern and controversy with respect to the development of live flavivirus vaccines. As an experimental system for investigating the ability of flavivirus genomes to recombine, we developed a "recombination trap," which was designed to allow the products of rare recombination events to be selected and amplified. To do this, we established reciprocal packaging systems consisting of pairs of self-replicating subgenomic RNAs (replicons) derived from tick-borne encephalitis virus (TBEV), West Nile virus (WNV), and Japanese encephalitis virus (JEV) that could complement each other in trans and thus be propagated together in cell culture over multiple passages. Any infectious viruses with intact, full-length genomes that were generated by recombination of the two replicons would be selected and enriched by end point dilution passage, as was demonstrated in a spiking experiment in which a small amount of wild-type virus was mixed with the packaged replicons. Using the recombination trap and the JEV system, we detected two aberrant recombination events, both of which yielded unnatural genomes containing duplications. Infectious clones of both of these genomes yielded viruses with impaired growth properties. Despite the fact that the replicon pairs shared approximately 600 nucleotides of identical sequence where a precise homologous crossover event would have yielded a wild-type genome, this was not observed in any of these systems, and the TBEV and WNV systems did not yield any viable recombinant genomes at all. Our results show that intergenomic recombination can occur in the structural region of flaviviruses but that its frequency appears to be very low and that therefore it probably does not represent a major risk in the use of live, attenuated flavivirus vaccines.


Freiburg school of ordoliberalism contributions to the modern economic thinking and some of its implications for post-war economic and social policy in West Germany are discussed in this paper. After explaining some elementary terms there is a short excursion in the economic history and external conditions. Part four discusses the importance of competition for both a dynamic and stabile economic growth performance and long-lasting balance in society, followed by a description of the basic premises of the competitive order - the constitutive principles and the regulatory principles preserving the competition and balance in long-run period. The role of state, science and the churches in creating and influencing both the order of economy and society is the theme of part five. Social market economy arising from the ordoliberal theoretical conception is discussed in part six.


. The increasing developments of wind power plants occur in many countries, which are used to mitigate the adverse effects of fossil fuels on the environment. In consideration of negative impacts, wind energy should be systematically analyzed in order to opti-mize the plans of governments and developers. A decision-making support system for wind power plant site selection was developed by using geographical information system in this study. The environmental, economic, and technical factors are invoked to generate the methodology. By comparing the overall performance index from the results, the best locations for wind power plants can be selected. The methodology was applied to the case study of Saskatchewan, where the development of wind power plant could be considered urgent. The results demonstrate that Saskatchewan has great potential for wind power energy development and southwest Saskatchewan is the most favorable area.


Chylous ascites is the accumulation of a milk-like peritoneal fluid rich in triglycerides and it is an unusual complication following surgical treatment of colorectal cancer. Conservative management is usually sufficient in patients with chylous ascites after surgery. However, we describe a patient with intractable chylous ascites after laparoscopic anterior resection for sigmoid colon cancer who failed initial conservative treatment. This patient was successfully managed by surgery.


The number of newly developed nanomaterials is steadily increasing but only a few are suitable for applications in biology. These nanomaterials are often made from harmful compounds and there is no convenient technique to remove them from the body after application. This study is focused on silicon nanocrystals and nanodiamonds, which are two promising nanomaterials for bio-applications. Silicon nanocrystals (Si-NCs) are exceptional since they provide several desired properties: low cytotoxicity, suitability for chemical activation, efficient photoluminescence, and bio-degradability. All these parameters promote application of Si-NCs in living organisms and even human medicine. Nanodiamonds (NDs), on the other hand, are non-biodegradable which limits their use to mostly long term in vitro studies. However, when using these nanomaterials one needs to address the effect of accumulation and aggregation of such materials in cells and how it contributes to the overall cytotoxicity. Here, we present studies on the interaction of two promising nanomaterials Si-NCs and NDs with actin structure of mammalian cells, evaluation of their cytotoxicity by various methods, and observation of single nanoparticle luminescence spectra within living cells. According to our results Si-NCs are more promising for application in nanomedicine compared to NDs.


Nonlinearities in the gravitational evolution, galaxy bias, and redshift-space distortion drive the observed galaxy density fields away from the initial near-Gaussian states. Exploiting such a non-Gaussian galaxy density field requires measuring higher-order correlation functions, or, its Fourier counterpart, polyspectra. Here, we present an efficient parallel algorithm for estimating higher-order polyspectra. Based upon the Scoccimarro estimator, the estimator avoids direct sampling of polygons using the fast Fourier transform, and the parallelization overcomes the large memory requirement of the original estimator. In particular, we design the memory layout to minimize the inter-CPU communications, which excels in the code performance.


Background Gaining communication skills with adolescents is a competency required by all paediatric trainees. Effective communication involves the ability to listen and empower adolescents to discuss and decide on sensitive or complex issues impacting on their health. Aims To gain communication skills with adolescents by doing school health visits that provide information about the hospital and facilitate discussion on health topics and life style issues raised by young people themselves. Methods Paediatric trainees carried out 2–3 school visits over 6 months during their child health rotation. Initially visits targeted a school for vulnerable adolescents at risk of school exclusion. Subsequently visits expanded to two mainstream schools. Workshops were discussed with schools and presented to parents and students as part of health promotion within Personal, Social, Health Education (PSHE) lessons. In pairs registrars did 45 min workshops introducing adolescents to their local paediatric team and hospital using different approaches, including a short video of the hospital. This was followed by a discussion on health and life style topics raised by the young people themselves. A self reporting semi-structured questionnaire was sent to all registrars involved to seek their views on the skills gained by participating in this project. Quantitative and qualitative analysis was carried out. Results To date 17 paediatric registrars over 2 years have participated in these school visits. A response rate of 100% was achieved. 90% considered they had gained skills to communicate effectively with adolescents;80% felt they had better understanding of how the school environment impacts on young people (including impact of peer relationships) and 80% considered they had been provided with an opportunity to participate in health education. Trainees' comments on their individual learning were categorised into different themes. The most common theme was the increased understanding of adolescents' needs and the training value of talking to adolescents in their own 'comfort' zone. Trainees suggested ideas to improve further the educational value of the school visits. Conclusion Paediatric trainees involved in school health workshops self-report gaining experience in competencies towards effective communication with adolescents. Trainees also considered that these school visits were a valuable learning opportunity to improve their understanding of young people's health needs.


The authors use the environment–strategy–performance theoretical framework to examine the direct influence of the environmental market conditions of competitive intensity and market dynamism on knowledge management capabilities of multinational corporation (MNC) subsidiaries and resultant subsidiary performance. The results of a survey of the managers of Croatian subsidiaries of foreign MNCs indicate that though both competitive intensity and market dynamism individually influence knowledge management capabilities, when examined jointly, market dynamism is a more influential environmental market condition than competitive intensity. The authors also find a significant, positive relationship between a subsidiary's knowledge management capabilities and its performance. The findings indicate the importance of understanding local market conditions and developing proper strategic configurations for MNC subsidiaries.


Poverty has a profound effect on child health (Fig. 1). The reported incidence of asthma, attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) is rising. Investigators studied data reported by parents to US National Survey of Children's Health in 2003, 2007 and 2011–2012, to determine if reported incidence is influenced differentially by poverty status. The lifetime prevalence of all three target disorders increased during the study period: asthma rose 18%, from 12.5% in 2003 to 14.6% in 2011–2012, ADHD rose 44%, from 6.9% in 2003 to 9.9% in 2011–2012, and ASD rose more than four-fold, from 0.5% in 2003 to 2.3% in 2011–2012. The rise in asthma lifetime prevalence was greatest in the poorest children at 25.8%, particularly uninsured children at 57.9%. The increase in lifetime prevalence of ADHD occurred comparably among all children regardless of poverty. In contrast, increases in the lifetime prevalence of ASD were greater in groups with more financial resources and those with private insurance. The rise was also significantly greater among adolescents, boys and white non-Hispanics. Poor US children are more likely than other US children to be diagnosed with asthma, but less likely to be diagnosed with autism.


An integrated portable USB based readout interface for the ATLAS semiconductor trackers (SCT) has been built. The ATLAS SCT modules are large area silicon strip detectors designed for tracking of high-energy charged particles resulting in collisions on Large Hadron Collider (LHC) in CERN. These modules can be also used on small accelerators for medical or industry applications where a compact and configurable readout interface would be useful. A complete custom made PC-host software tool was written for Windows platform for control and DAQ with build-in online visualization. The new constructed interface provides integrated power, control and DAQ and configurable communication between the detector module and the controlling PC. The interface is based on the Field Programmable Gate Array (FPGA) and the high speed USB 2.0 standard. This design permits to operate the modules under high particle fluence while minimizing the dead time of the whole detection system. Utilization of the programmable device simplifies the operation and permits future expansion of the functionality without any hardware changes. The device includes the high voltage source for detector bias up to 500 V and it is equipped with number of devices for monitoring the operation and conditions of measurement (temperature, humidity, voltage). These features are particularly useful as the strip detector must be operated in a well controlled environment. The operation of the interface will be demonstrated on data measured with different particles from radiation sources.


Using recently developed methods for the evaluation of five-loop amplitudes in perturbative QCD, corrections of order alphas4 for the nonsinglet part of the cross section for electron-positron annihilation into hadrons and for the decay rates of the Z boson and the tau lepton into hadrons are evaluated. The new terms lead to a significant stabilization of the perturbative series, to a reduction of the theory uncertainly in the strong coupling constant alphas, as extracted from these measurements, and to a small shift of the central value, moving the two central values closer together. The agreement between two values of alphas measured at vastly different energies constitutes a striking test of asymptotic freedom. Combining the results from Z and tau decays we find alphas(MZ)=0.1198+/-0.0015 as one of the most precise and presently only result for the strong coupling constant in order alphas4.


Counterfeiting of valuable certificates, documents, and banknotes is a serious issue worldwide. As a result, the need for developing novel anticounterfeiting materials is greatly increasing. Herein, we report a new kind of ultralong hydroxyapatite nanowire (HAPNW)-based paper with luminescence, fire resistance, and waterproofness properties that may be exploited for anticounterfeiting applications. In this work, lanthanide-ion-doped HAPNWs (HAPNW:Ln3+) with lengths over 100 μm have been synthesized and used as a raw material to fabricating a free-standing luminescent, fire-resistant, water-proof paper through a simple vacuum filtration process. It is interesting to find that the luminescence intensity, structure, and morphology of HAPNW:Ln3+ highly depend on the experimental conditions. The as-prepared HAPNW:Ln3+ paper has a unique combination of properties, such as high flexibility, good processability, writing and printing abilities, luminescence, tunable emission color, waterproofness, and fire resistance. In addition, a well-designed pattern can be embedded in the paper that is invisible under ambient light but viewable as a luminescent color under ultraviolet light. Moreover, the HAPNW:Ln3+ paper can be well-preserved without any damage after being burned by fire or soaked in water. The unique combination of luminescence, fire resistance, and waterproofness properties and the nanowire structure of the as-prepared HAPNW:Ln3+ paper may be exploited toward developing a new kind of multimode anticounterfeiting technology for various high-level security antiforgery applications, such as in making forgery-proof documents, certificates, labels, and tags and in packaging.


SRA's proprietary product, NameTag TM, which provides fast and accurate name recognition, has been reused in many applications in recent and ongoing efforts, including multilingual information retrieval and browsing, text clustering, and assistance to manual text indexing. This paper reports on SRA's experience in embedding name recognition in these three specific applications, and the mutual impacts that occur, both on the algorithmic level and in the role that name recognition plays in user interaction with a system. In the course of this, we touch upon various interactions between proper name recognition and machine translation (MT), as well as the role of accurate name recognition in improving the performance of word segmentation algorithms needed for languages whose writing systems do not segment words. 1 I n t r o d u c t i o n Fast and accura te name recognition products are only now coming onto the market. SRA's proprietary product, NameTag, has been reused in many applications in recent and ongoing efforts, including multilingual information retrieval and browsing, text clustering, and assistance to manual text indexing. In the following paper, we report on our experience in embedding name recognition in these, three specific applications, as well as the mutual impacts that occur, both on the algorithmic level and in the role that name recognition plays in user interaction with a system. In the course of this, we touch upon various interactions between proper name recognition and machine translation (MT), as well as the role of accurate name recognition in improving the performance of word segmentation algorithms needed for languages such as Japanese. Name recognition clearly offers added value when integrated with other algorithms and systems, but the latter also affect the way in which name recognition is performed, specifically the choice of high-recall or high-precision strategies. But first, we discuss the relevant features of NameTag. 2 D e s c r i p t i o n o f N a m e T a g NameTag is a multilingual name recognition system. It finds and disambiguates in texts the names of people, organizations, and places, as well as time and numeric expressions with very high accuracy. The design of the system makes possible the dynamic recognition of names: NameTag does not rely on long lists of known names. Instead, NameTag makes use of a flexible pattern specification language to identify novel names that have not been encountered previously. In addition, NameTag can recognize and link variants of names in the same document automatically. For instance, it can link "IBM" to "International Business Machines" and "President Clinton" to "Bill Clinton." NameTag incorporates a language-independent C-t-+ pattern-matching engine along with the language-specific lexicons, patterns, and other resources necessary for each language. In addition, the Japanese, Chinese, and Thai versions integrate word segmenters to deal with the orthographic challenges of these languages. (NameTag currently has these language versions available plus ones for English, Spanish, and French.) NameTag is an extremely fast and robust system that can be easily integrated with other applications through its API. It has been our experience that NameTag has lent itself to so many successful integrations in diverse applications not just due to its accuracy, but to its speed. (Its NT version is currently benchmarked at 300 megabytes/hour on a Pentium Pro.) It is an attractive package to embed in an application, as it does not cause significant retardation of performance. In the following discussion, we refer to various versions of NameTag, most prominently systems for English and Japanese. Their extraction accuracy varies. For example, in the Sixth Message Understanding Conference (MUC-6), the English systern was benchmarked against the Wall Street Journal blind test set for the name tagging task, and achieved a 96% F-measure, which is a combination ot" recall and precision measures. Our internal testing of the Japanese system against blind test sets of w~rious Japanese newspaper articles indicates that it achieves from high-80 to 1ow-90% accuracy, depending on the types of corpora. Indexing names in Japanese texts is usually more challenging than English for two main reasons. First, there is no case distinction in .Japanese, whereas English names in newspapers are capitalized, and capitalization is a very strong clue for English name tagging. Second, Japanese words are not separated by spaces and therefore must be segmented into separate words before the name tagging process. As segmentation is not 100% accurate, segmentat ion errors can sometimes can use name tagging rules not to fire or to misfire. 3 P r o p e r N a m e R e c o g n i t i o n I n t e g r a t e d W i t h a B r o w s i n g & R e t r i e v a l S y s t e m We have recently developed a system incorporating NarneTag tha t allows monolingual users to access information on the World Wide Web in languages that they do not know (Aone, Charocopos, and Gorlinsky, 1997). For example, previously it was not easy for a monolingual English speaker to locate necessary information writ ten in Japanese. The user would not know the query terms in Japanese even if the search engine accepted Japanese queries. In addition, even when the users located a possibly relevant text in Japanese, they would have little idea about what was in the text. Output of off-the-shelf machine translat ion (MT) systems are often of low quality, and even "high-end" MT systems have problems part icularly in translat ing proper names and specialized domain terms, which often contain the most critical information to the users. Now these users have available our multilingual (or cross-linguistic) information browsing and retrieval system, which is aimed at monolingual users who are interested in information from multiple language sources. The system takes advantage of namerecognition software as embodied in NameTag to improve the accuracy of cross-linguistic retrieval and to provide innovative methods t.o browse and explore multi l ingual document collections. The system indexes texts in different languages (currently English and Japanese) and allows the users to retrieve relevant texts in their native language (currently English). The retrieved text is then presented to the users with proper names and specialized domain terms t ranslated and hyperlinked. Among the innovations in our system is the stress placed upon proper names and their role as indices for document content. The system consists of an Indexing Module, a Client Module, and a Term Translat ion Module. The Indexing Module creates and inserts indices into a database while the Client, Module allows browsing and retrieval of information in the database through a Web-browser-based graphical user interface ((~ IJ l). The Term Translation Module dynamical ly translates English user queries into Japanese and the indexed terms in retrieved Japanese documents into English. T h e I n d e x i n g M o d u l e For the present application, the system indexes names of people, entities, and locations, as well as scientific and technical (S&T) terms in both English and Japanese texts, and allows the user to query and browse the indexed database in English. As NameTag processes texts, the indexed terms are stored in a relational database with their semantic type information (person, entity, place, S&T term) and alias information along with such meta da ta as source, date, language, and frequency information. T h e C l i en t M o d u l e The Client Module lets the user both retrieve and browse information in the database through the Web-browser-based GUI. In the query mode, a formbased Boolean query issued by a user is au tomat i cally translated into an SQL query, and the English terms in the query are sent to the Term Translat ion Module. The Client Module then retrieves documents which match either the original English query or the translated .Japanese query. As the indices are names and terms which may consist of multiple words (e.g., "Warren Christopher," "memory chip"), the query terms are delimited in separate boxes in the form, making sure no ambigui ty occurs in both translation and retrieval. In its browsing mode, the Client Module allows the user to browse the information in the database in various ways. For example, once the user selects a particular document for viewing, the client sends it to an appropriate (i.e., English or Japanese) indexing server for creating hyperlinks for the indexed terms, and, in the case of a Japanese document , sends the indexed terms to the Term Translat ion Module to translate the Japanese terms into English. The result that the user browses is a document each of whose indexed terms are hyperlinked to other documents containing the same indexed terms. Since hyperlinking is based on the original or t ranslated English terms, the monolingual English speaker can follow the links to both English and .Japanese documents transparently. In addition, the Client Module is integrated with a commercial MT sys tem for a rough translation of the whole text. T h e T e r m T r a n s l a t i o n M o d u l e The Term Translation Module is used by the Client Module bi-directionally in two different modes. Tha t is. it translates English query terms into Japanese in the query mode and, in reverse, translates Japanese indexed terms into English for viewing of a retrieved Japanese text in the browsing mode. 3.1 I s sues C o n c e r n i n g P r o p e r N a m e R e c o g n i t i o n fo r B r o w s i n g a n d R e t r i e v a l Based on the system description above in the preceding sections, we describe in more detail in the following the impacts of name recognition on multilingual browsing and retrieval. 3.1.1 I n d e x i n g A c c u r a c y To index, the system uses two different configurations of NameTag for English and Japanese. Indexing of names is particul


The paper introduces a new way of understanding the web graphics phenomenon. We based it on the popular culture approach by M. Bakhtin. We introduce and exemplify the categories of ambiguous messages created and communicated by web graphics. The discussion on coding of ambiguous information is given. Revolution in multimedia requires completing conventions in information coding. One day, the paradigm of unambiguous meaning of coded information will be attacked by the needs of coding of ambiguous meaning. The paper proposes one way how to code the ambiguity. For transparent illustration only the comic information is used (but not defined). One possible way of visualization of structure of coded comic information is shown. The implication for user interface is discussed. Sharing of ambiguous visual content is undoubtedly one of the prominent Web-based graphics applications.


The beef supply chain in Indonesia is a long and challenging (complex) chain because it involves many actors to track beef, from breeders in the form of cattle to a slice of meat consumed by consumers. The openness (transparency) of each actor involved in the supply chain can increase the safety of beef consumed, ensuring food safety. To ensure food safety, a system is needed to make it easier for consumers to trace the origin of beef. This study discusses the infrastructure design of an information technology (IT) based beef supply chain traceability system. The design is carried out with a systems approach, where system requirements are identified based on the characteristics of the supply chain. The system modelling concept uses Unified Modelling Language (UML) and Entity Relationship (ER) Diagram combined with the Computer Based Information System (CBIS) concept to design a traceability system in the beef supply chain. The study results are a conceptual design for a traceability system infrastructure that can be developed to build a web-based traceability system.


Background: Cigarette smoking is the leading preventable cause of mortality in the world and the main risk factor for lung and head and neck cancer. E-cigarettes (ECs) are battery-operated devices that deliver nicotine via inhaled aerosols. Although ECs are marketed as a less harmful alternative to tobacco cigarettes and a smoking cessation aid, the health risks posed by exposure to EC aerosols are unknown. Nonetheless, the use of ECs has increased exponentially since 2003, with EC users reporting inhaling on average 200 puffs a day. EC aerosols have been reported to contain variable levels of genotoxins, including carcinogenic substances and reactive oxygen species (ROS). Some toxins in EC aerosols have been reported to reach the levels of similar to those in tobacco smoke. However, the genotoxicity of EC aerosols has not been characterized. Aims: (1) To determine the cytotoxicity and genotoxicity of short and long-term exposure to EC aerosols on human epithelial normal and cancer cell lines. (2) To evaluate whether exposure of EC aerosols modifies the cellular total antioxidant capacity (TAC). Methods: EC extracts were prepared from NJOY (12 or 18 mg/ml of nicotine) and Oakley eGo-T (0, 12 or 18 mg/ml of nicotine). Standard tobacco extracts were used for comparison. To assess the effects of short-term exposure, human epithelial normal (NuLi-1) and cancer (UD-SCC1) cell lines were exposed for 1 hour to various EC extract concentrations. To assess the effects of long-term exposure, cells lines were exposed every other day for 2 weeks to EC extracts. Cytotoxicity, DNA damage and TAC were evaluated at 1 h and 2 weeks. Cell viability was determined by MTT assay. DNA damage was quantified using the primer anchored DNA damage detection assay (PADDA). TAC was determined by the Antioxidant Assay Kit (Cayman). Data were analyzed by Student9s t-test. Results: At the range of EC extract concentrations used in this study and expected to occur in EC users (1 to 100 puffs/5 L of blood), no cytotoxicity was observed for either normal or cancer cells. However, significant levels of DNA damage were observed in cancer cells exposed to 10 or more puffs/5 L of EC extracts and in normal cells exposed to100 puffs/5 L. Long-term exposure to EC extracts resulted in a significant decrease in TAC, a measure of free radical scavengers. Conclusion: Even short-term exposure to low levels of EC aerosols can cause significant DNA damage. Our study emphasizes the need to further investigate the carcinogenic potential of EC aerosols and highlights the importance of regulating EC use. Grant support: This work was supported by the Oklahoma Tobacco Research Center (LQ). Dr. Queimado holds a Presbyterian Health Foundation Endowed Chair in Otorhinolaryngology. Citation Format: Vengatesh Ganapathy, Jimmy Manyanga, Lacy Brame, David Rubenstein, Theodore L. Wagener, Ilangovan Ramachandran, Lurdes Queimado. Electronic cigarettes induce significant DNA damage and reduce cellular antioxidant levels. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3593.


Spiders spin their silk from an aqueous solution to a solid fiber in ambient conditions. However, to date, the assembly mechanism in the spider silk gland has not been satisfactorily explained. In this paper, we use molecular dynamics simulations to model Nephila clavipes MaSp1 dragline silk formation under shear flow and determine the secondary structure transitions leading to the experimentally observed fiber structures. While no experiments are performed on the silk fiber itself, insights from this polypeptide model can be transferred to the fiber scale. The novelty of this study lies in the calculation of the shear stress (300-700 MPa) required for fiber formation and identification of the amino acid residues involved in the transition. This is the first time that the shear stress has been quantified in connection with a secondary structure transition. By study of molecules containing varying numbers of contiguous MaSp1 repeats, we determine that the smallest molecule size giving rise to a "silk-like" structure contains six polyalanine repeats. Through a probability analysis of the secondary structure, we identify specific amino acids that transition from α-helix to β-sheet. In addition to portions of the polyalanine section, these amino acids include glycine, leucine, and glutamine. The stability of β-sheet structures appears to arise from a close proximity in space of helices in the initial spidroin state. Our results are in agreement with the forces exerted by spiders in the silking process and the experimentally determined global secondary structure of spidroin and pulled MaSp1 silk. Our study emphasizes the role of shear in the assembly process of silk and can guide the design of microfluidic devices that attempt to mimic the natural spinning process and predict molecular requirements for the next generation of silk-based functional materials.


This paper has its background in a research project that studied 12 cases of local development and co‐operation in the Swedish wood‐manufacturing sector during 1997‐2000 and 20 similar projects in other parts of Sweden in 1998. One reflection from this project was that the small firm managers, as well as the supporting bodies, lacked understanding of the process of the creation and support for survival of the networks. This article presents some hypotheses of the important factors in the creation process of strategic small to medium‐sized enterprise (SME) networks. This is done through an in‐depth analysis over the whole life cycle (eight years) for one of the networks studied in the project. The article gives small business owners some ideas of what they should consider before they start or join an attempt to create a strategic SME business network, indicates some of the pitfalls and contributes to policymakers' understanding of what kind of support is needed.


We are observing with great concern the global spread of the COVID19 Pandemic. What is equally alarming is a less visible, albeit serious Public health issue; one that the United Nations has dubbed as the 'Shadow Pandemic' [1]. This is none other than the globally prevalent issue of violence against women, particularly Intimate Partner Violence.
Intimate Partner Violence (IPV) is a serious, possibly preventable public health problem globally. Pakistan ranks among the countries with the highest IPV rates [2]. On 11th March 2020, the World Health Organization declared the highly infectious and lethal Severe Acute Respiratory Syndrome Coronavirus 2 (COVID-19) to be a pandemic [3]. Drastic measures were enforced universally to curb the spread of COVID-19. Countries issued strict nationwide lockdowns to isolate the population and implemented social distancing. The economy was impacted tremendously, and many people experienced financial and emotional hardship during this mandatory confinement. While everyone was affected, one population was in a far worse situation than others. Survivors of IPV were trapped alongside their perpetrators and faced difficulty/less freedom to escape threatening situations compared to the past.
It is not surprising given that historical periods of uncertainty such as war or economic crisis have resulted in increased interpersonal violence, including violence against women [4].  The Hubei province of China, the first region to undergo a lockdown, saw nearly a doubling of their rates of IPV with the start of COVID19 Pandemic.  Similarly, tragic stories gained nationwide coverage in the United States. IPV may also have risen in Pakistan, even if it is not being covered as extensively.
During pandemics, fear causes us to minimize our personal needs and make sacrifices we would not normally make. This could be a reasonable approach for most but should not be for survivors of IPV. IPV survivors live in constant fear for themselves and their children; they are now devoid of their only means of mitigation; avoidance. Local woman's support groups in Pakistan should act and spread awareness about this grim reality hiding underneath the Pandemic. Resources/funding should be made available for survivors to be able to reach out for support without having to leave the watchful eyes of their perpetrators. Public health officials ought to investigate and document the rise in IPV to help identify the leading causes of the increase. These steps will assist in developing crisis-specific guidelines to provide adequate resources for the future. Continuous....


The design of an almost fully integrated phase-cut dimmer is presented. The circuit was designed on a 1um ultra high voltage (UHV) MOS technology in a silicon-on-insulator (SOI) wafer. The dimmer can operate with a duty cycle of up to 95% power (80%) and a load of up to 100 W which is adequate for modern domestic dimmable LED lights. The total occupied silicon area is 6.5 mm2 without pads.


The convergence of many proximal algorithms involving a gradient descent relies on its Lipschitz constant. To avoid computing it, backtracking rules can be used. While such a rule has already been designed for the forward-backward algorithm (FBwB), this scheme is not flexible enough when a non-differentiable penalization with a linear operator is added to a constraint. In this work we propose a backtracking rule for the primal-dual scheme (PDwB), and evaluate its performance for the epigraphical constrained high dynamical reconstruction in high contrast polarimetric imaging, under TV penalization.


Glaciers depicted on old maps reveal their historical extents, before the advent of aerial and satellite remote sensing. Digital glacier inventories produced from these maps can be employed in assessments of centennial-scale glacier change. This study reconstructs the ~1899 (covering the period 1882–1916) glacier extent in Nordland, northern Norway, from historical gradteigskart maps, with an emphasis on examining the accuracy of the mapped glaciers. Glacier outlines were digitised from georectified scans of the analogue maps in a raster graphics editor and were subsequently inventoried in a GIS. The accuracy of the historical glacier extent was established from written descriptions and landscape photographs created during the original field surveys, and further validated against independent glacier outlines of (1) the maximum Little Ice Age extent derived from geomorphological evidence, and (2) the 1945 extent derived from vertical aerial photographs. An overall uncertainty of ±17% is associated with our inventory. Nordland's glaciers covered an area of 1712 ± 291 km2 in 1899. By 2000, total ice cover had decreased by 47% (807 ± 137 km2) at a rate of 6% 10 a−1 (80 ± 14 km2 10 a−1). The approach presented here may serve as a blueprint for future studies intending to derive glacier inventories from historical maps.


Curating boats can be difficult. They are complex structures, often demanding to conserve whether in or out of the water; they are usually large, difficult to move on land, and demanding of gallery space. Communicating life on board to a visiting public in the terra firma context of a museum can be difficult. Boats in their native environment are inherently dynamic artifacts. In a museum they can be static and divorced from the maritime context that might inspire engagement. New technologies offer new approaches to these problems. 3D laser scanning and digital modeling offers museums a multifaceted means of recording, monitoring, studying and communicating watercraft in their care. In this paper we describe the application of 3D laser scanning and subsequent digital modeling. Laser scans were further developed using computer-generated imagery (CGI) modeling techniques to produce photorealistic 3D digital models for development into interactive, mediabased museum displays. The scans were also used to generate 2D naval lines and orthographic drawings as a lasting curatorial record of the dhows held by the National Museum of Qatar.


Data communications between producer instructions and consumer instructions through memory incur extra delays that degrade processor pe rformance. In this paper, we introduce a new storage media with a novel addressing mechanism to avoid address calculations. Instead of a memory address, each load and store is assigned a s ignature for accessing the new storage. A signature consists of the color of the base registe r along with its displacement value. To represent distinct register content, a unique color is assign ed to a register whenever the register is updated. When two memory instructions have the same signature, they address to the same memory location. This memory signature can be formed early in the processor pipeline. For fast data communication, a small Signature Buffer, addressed by the memory signature, can be established to permit stores and loads bypassing normal memory hierarchy. Performance evaluations based on an Alpha 21264-like pipeline using SPEC2000 benchmarks show that an IPC (Instruction-PerCycle) improvement of 12-17% is possible using a small 8-entry signature buffer.


The green fluorescent protein GFPuv has been genetically engineered to investigate the influence of N‐terminal tyrosine extensions in aqueous two‐phase systems. Fusions in the N‐terminus affected the protein expression, and tags containing three tyrosines and prolines influenced the expression favorably. This effect is probably due to changes in mRNA stability, because the amounts of corresponding mRNAs correlated with the amounts of GFPuv proteins. The partitioning was investigated in two different aqueous two‐phase systems, a two‐polymer system composed of EO30PO70/dextran and a PEG/salt system with potassium phosphate. Partitioning in the PEG/salt system generally was more favorable than in the EO30PO70/dextran system. Tags with three tyrosines resulted in higher partitioning toward the EO30PO70‐ and PEG‐rich phases, respectively. The effect of adding proline residues to the tag was also investigated, and the partitioning effect of the tag was enhanced when prolines were included in the tags with three tyrosines. The best tyrosine tag, Y3P2, increased the partition coefficient 5 times in the PEG/salt system. Thermoseparation of the EO30PO70 phase allowed recovery of 83% Y3P2‐GFPuv protein in a water phase.


Using an asymmetric associative network with synchronous updating, it is possible to recall a sequence of patterns. To obtain a stable sequence generation with a large storage capacity, we introduce a threshold that eliminates the contribution of weakly correlated patterns. For this system we find a set of evolution equations for the overlaps of the states with the patterns to be recognized. We solve these equations in the limit of the stationary cycle, and obtain the critical value of the capacity as a function of the threshold and temperature. Finally, a numerical simulation is made, confirming the theoretical results.


Objectives With disease-modifying drugs on the horizon for degenerative ataxias, ecologically valid motor biomarkers are highly warranted. In this observational study, we aimed to unravel and validate markers of ataxic gait in real life by using wearable sensors. Methods We assessed gait characteristics of 43 patients with degenerative cerebellar disease (Scale for the Assessment and Rating of Ataxia [SARA] 9.4 ± 3.9) compared with 35 controls by 3 body-worn inertial sensors in 3 conditions: (1) laboratory-based walking; (2) supervised free walking; (3) real-life walking during everyday living (subgroup n = 21). Movement analysis focused on measures of spatiotemporal step variability and movement smoothness. Results A set of gait variability measures was identified that allowed us to consistently identify ataxic gait changes in all 3 conditions. Lateral step deviation and a compound measure of spatial step variability categorized patients vs controls with a discrimination accuracy of 0.86 in real life. Both were highly correlated with clinical ataxia severity (effect size ρ = 0.76). These measures allowed detecting group differences even for patients who differed only 1 point in the clinical SARAposture&gait subscore, with highest effect sizes for real-life walking (d = 0.67). Conclusions We identified measures of ataxic gait that allowed us not only to capture the gait variability inherent in ataxic gait in real life, but also to demonstrate high sensitivity to small differences in disease severity, with the highest effect sizes in real-life walking. They thus represent promising candidates for motor markers for natural history and treatment trials in ecologically valid contexts. Classification of evidence This study provides Class I evidence that a set of gait variability measures, even if accessed in real life, correlated with the clinical severity of ataxia in patients with degenerative cerebellar disease.


Traditional text classifiers are limited to predicting over a fixed set of labels. However, in many real-world applications the label set is frequently changing. For example, in intent classification, new intents may be added over time while others are removed. We propose to address the problem of dynamic text classification by replacing the traditional, fixed-size output layer with a learned, semantically meaningful metric space. Here the distances between textual inputs are optimized to perform nearest-neighbor classification across overlapping label sets. Changing the label set does not involve removing parameters, but rather simply adding or removing support points in the metric space. Then the learned metric can be fine-tuned with only a few additional training examples. We demonstrate that this simple strategy is robust to changes in the label space. Furthermore, our results show that learning a non-Euclidean metric can improve performance in the low data regime, suggesting that further work on metric spaces may benefit low-resource research.


This chapter addresses a phenomenon of wide significance for past and future agricultural potential – landesque capital. This is understood as investments made in land with an anticipated life beyond that of the present crop, or crop cycle. Irrigation canals and agricultural terraces are the most obvious forms of landesque capital, but the clearance of stones and the improvement of agricultural soils over the years are other, albeit less spectacular, examples. It is argued, that alongside the more obvious factors of climate and soil, the distribution of landesque capital – and hence the history of land use – is as an important factor in understanding global differences in the productivity of agricultural lands. The occurrence of landesque capital has, over the years, been explained from a number of different perspectives: as a direct or indirect reflection of semi-arid and arid lands, as the result of diffusion, as a consequence of historical 'siege' situations, or as resulting from the accumulation strategies of chiefdoms and empires. It is argued that most of these general approaches to the explanation of landesque capital make the mistake of not fully taking into account the spatial aspect of landesque capital. They tend to reflect an historic and economic rather than a geographical understanding of investments. Unlike monetary capital, which is fluid in space but fixed in time, landesque capital is fixed in space but "fluid" in time. The chronological and social contexts of its use, management and further development, can differ significantly from the contexts that once shaped it.


The efficient export of a subset of Escherichia coli envelope proteins is dependent upon the product of the secB gene. Previous studies indicated that SecB promotes the export of the periplasmic maltose-binding protein (MBP) by preventing premature folding of the precursor MBP in the cytoplasm into an export-incompetent form. In this study, SecB has been purified to homogeneity and shown to be a soluble, cytoplasmic, multimeric protein composed of identical 17-kDa subunits. SecB was required for efficient in vitro translocation of MBP into inverted membrane vesicles. The addition of purified SecB to an in vitro system prepared from SecB- cells significantly enhanced MBP translocation. The purified protein also quantitatively retarded folding of precursor MBP into a stable, protease-resistant conformation in the absence of membranes. Finally, the inclusion of excess purified SecB in a SecB+ in vitro system significantly prolonged the time in which precursor MBP remained competent for posttranslational import into membrane vesicles.


The R&D group at Paramax Systems Canada is working on a demonstration model of a multi- sensor data fusion (MSDF) implementation for the Canadian Patrol Frigate. The conditions are made very realistic by the use of the Software Test and Development Facility's situated on the premises in Montreal. The development is done on a SUN SPARC-10. The inputs are read from a Shipboard Integrated Processing and Display System bus via a monitor node and an interface card. The program consists of multiple separate UNIX processes communicating via the Inter Process Communication protocol. For evaluation purposes, two databases are updated corresponding to the MSDF and the usual tracking. The program fuses the tracks provided by the sensors as if they were contacts. The paper describes the overall MSDF design as well as the tracking and identification algorithms used in the project. The necessary compromises that were made are presented with explanations. A discussion of the expected results is included. The paper ends with the improvements that are already foreseen.


The master's thesis deals with the question of text complexity in a reading event. By reading literary texts at a reading event, the reading comprehension mentor gets important insights into the pupil's response to the text. Readers or listeners of different ages can namely understand the same text, but of course, differently (see Saksida, 2009). In the master's thesis, we focused on pupils' responses to more demanding literary texts using the long reading method.
Reading comprehension mentors play an important role in the reading of a young reader. In the theoretical part, we relied on three important questions to which the reading comprehension mentor has to know the answer to why, what, and how to read texts at school. The question of why we read is answered by the definition of literacy. With the question of what to read, we linked the reading motivation, the reading interest, and the positive attitude to reading. A reading comprehension mentor has to proceed from pupils' reading interest, but he should not emphasize it too much, since reading the texts at a reading event does not mean reading anything, that is, reading only for pleasure. Also reading the texts at a reading event requires deep reading and conversation about the read. In the master's thesis, we emphasized more demanding texts, which students can be offered to read (better more demanding than too simple texts), but we need to discuss exhaustively on the more demanding spots in the texts. We have defined the question of how to read by reading strategies, as they are related to reading and talking about what we read. We described a model for the development of reading ability, which we divided into the mentor's preparation for the school interpretation of the belletristic text and on the stages of school interpretation of the belletristic text. We attached great importance to the verification of all cognitive levels, both higher and lower, and in details described Bloom's classification, which teachers use to the maximum extent. We presented the method of long reading, which creates encouraging positions in which pupils spontaneously slide into the world of literature. In our study, we read the book Happy King and Other Fairy Tales written by Oscar Wilde to the pupils of the first educational period, therefore we presented the author and the book of fairy tales itself, showed the position of the book in the curriculum, and stated the goals that can be realized with fairy tales in the first educational period.
In the empirical part, we verified the fact that the same text can be understood by listeners of different ages, but differently. The pupils of the first, second and third class of Utik Affiliate School participated in the empirical work. With the study we wanted to check the response of students to more demanding literary texts – The Happy Prince, The Nightingale and the Rose, The Selfish Giant and The Devoted Friend. We read the fairy tales using the long reading method and found that this method is definitely suitable for reading longer and more complex texts. The method was constantly increasing the tension, raising the motivation for listening to fairy tales, and it has made it possible for us to discuss exhaustively the more demanding points in the text.
Perfectly appropriate responses of some students to more demanding texts led us to the conclusion that solid and unambiguous classification of children's texts into closed age groups
is unnecessary. More time should be devoted to the very development of the ways in which readers recall the text.
Similarly, the reading comprehension mentor should adjust the content, goals and methods of the reading event, especially for more capable (gifted) pupils by offering them a slightly more demanding text and different levels of reading tasks.


One of the recent trends in dealing with the concept of lying has been to argue that the idea that one needs to deceive someone in order to lie has been accepted too hastily. In Lying and Insincerity Stokke shares this opinion and proposes a de fi nition of lying based on the notion of common ground that includes bald-faced lies. Additionally, he rejects the idea that lying can be accomplished with pragmatic means such as conversational implicatures and proposes a formal distinction between lying and misleading. In this review, I present the content of Stokke's book and critically discuss the two points mentioned above.


The Triassic-Jurassic boundary interval (ca. 201 Ma) was a time of sudden global environmental changes triggered by Pangea breakup and Central Atlantic Magmatic Province (CAMP) development. The bulk-rock mineralogy, clay mineralogy and major element geochemistry of 87 continental mudrock samples collected from four borehole cores yield information on  Rhaetian - earliest Hettangian palaeoclimatic changes in the Polish Basin. During the Rhaetian, smectite preponderance was replaced by kaolinite and illite domination. This fundamental shift in clay mineral assemblages (supported by major element data) indicates very significant change in climate humidity. Moreover, some beds in the Zagaje Formation (Upper Rhaetian – Lower Hettangian) are particularly rich in kaolinite indicating extreme chemical weathering in humid-subtropical to tropical climate episodes in the aftermath of powerful warming and abundant rainfall. Importantly, the first distinct kaolinite enrichment appears already in the lower Rhaetian Wielichowo Beds. In addition, abrupt and episodic shifts in the kaolinite-illite ratio and in values of weathering indices point to profound climate destabilisation and a sequence of frequent, catastrophic climatic reversals in the Late Rhaetian and at the Triassic-Jurassic boundary. These results are generally consistent with carbon isotope records in sections worldwide.


Radiotherapy is an essential component of cancer therapy. Despite advances in cancer genomics, the mutation signatures of radioresistant tumors have not yet been fully elucidated. To address this issue, we analyzed a unique set of clinical specimens from a uterine cervical cancer that repeatedly locally recurred after multiple rounds of radiotherapy. Exon sequencing of 409 cancer-related genes in the treatment-naïve tumor and the tumors that recurred after initial and secondary radiotherapy identified (i) activating mutations in PIK3CA and KRAS, and putative inactivating mutations in SMAD4, as trunk mutation signatures that persisted over the clinical course; and (ii) mutations in KMT2A, TET1, and NLRP1 as acquired mutation signatures observed only in recurrent tumors after radiotherapy. Comprehensive mining of published in vitro genomics data pertaining to radiosensitivity revealed that simultaneous mutations in KRAS and SMAD4, which have not been described previously in uterine cervical cancer, are associated with cancer cell radioresistance. The association between this mutation signature and radioresistance was validated by isogenic cell-based experiments. These results provide proof-of-principle for the analytical pipeline employed in this study, which explores clinically relevant mutation signatures for radioresistance, and demonstrate that this approach is worth pursuing with larger cohorts in the future.


We study the long-termchange of the amplitude of the first (27-day, A27) and second (14-day, A14) harmonics of the galactic cosmic rays (GCR) recurrent variation connected to the solar rotation period. Using two high-latitude neutron monitors, Oulu and Apatity, we verify the dominant 11-year cycle in A27 and A14 and their systematic 22-year variation (Hale cycle) during sunspot minima, with higher values during the positive polarity (A > 0) minima than during negative (A< 0). We show that the A27 and A14 amplitudes during sunspot minima exhibit a slight declining trend. We suggest that this declining trend is due to the weakening of the solar polar magnetic field during the previous four solar cycles and the ensuing latitudinal widening of the heliospheric current sheet (HCS) region. After trend removal the amplitudes of the 22-year variation increase, and are typically about 15-30 % for A27 and about 30-45% for A14. Here we quantify the 22-year cyclicity in A27 and A14 in a robust way for last five solar minima and give a physical explanation to the earlier ideas about the effect of drifts to produce the observed phase of the 22-year cyclicity.


The influence of suppository bases and adjuvants on the release rate of drugs and the absorption of non-absorbable drugs such as sulfanilic acid (SA) and sulfaguanidine (SG), was investigated following the rectal administration of suppositories. The suppository bases used were lipophilic bases such as Witepsol W 35, H 15, S 55, E 75 and hydrophilic base such as macrogol. SA was rapidly released from macrogol, W 35, H 15 and S 55, except E 75. On the other hand, SG was rapidly released from macrogol, whereas the release of SG from lipophilic bases was slow. Rectal absorption of SA and SG following administration of each drug alone in suppository form was slight. On the addition of diclofenac sodium (DF) as absorption promoter the blood levels of SA and SG released from all suppositories increased by about two to four fold compared with those suppositories containing only SA or SG, respectively. However, the absorption of SG still did not attain sufficient levels by the administration of DF only. The rectal absorption of SG was markedly increased by the release rate of the drug from the suppository. These results indicate that after administration of these suppositories the bioavailability of non-absorbable drugs was sufficiently improved by enhancing both the release rate from the suppositories and the rectal membrane permeability.