This study was designed to examine the in vitro antibacterial and antioxidant activities of the essential oils (EOs) of Thymus satureioides (T.s) and T. pallidus (T.p). EOs were isolated by steam distillation and analyzed by capillary gas chromatography and gas chromatography coupled to mass spectrometry (GC–MS). The major constituents of the volatile fraction of T. satureioides were borneol (29.5%), carvacrol (9.1%), and β-caryophyllene (8.2%), while those of T. pallidus were camphor (29.8%), dihydrocarvone (17.6%), borneol (7.6%) and camphene (7.5%). The essential oils were tested against a panel of Gram+ and Gram- bacteria by using agar diffusion and broth dilution methods. The data indicated that the Gram-positive Bacillus subtilis was the most sensitive strain producing an average inhibition zone of 51.7 mm. Furthermore, Pseudomonas aeruginosa, known as a resistant strain, was also sensitive. The samples were also subjected to screening for their possible antioxidant activity by using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. The IC50 values of the oil of T. satureioides and T. pallidus were 0.32 and 11.6 mg/mL, respectively.


Background: Trastuzumab-or lapatinib-based therapies are recommended by the National Comprehensive Cancer Network (NCCN) guidelines as preferred agents for metastatic HER2-positive breast cancer. Few studies have compared treatment patterns, healthcare resource utilization (HRU), and costs in metastatic breast cancer (MBC) patients receiving trastuzumab vs. lapatinib. The objective of this study was to compare discontinuation rates, HRU, and costs in MBC patients (pts) initiated on trastuzumab vs. lapatinib. Methods: MBC adult women initiated on trastuzumab or lapatinib on/after 03/13/2007 (lapatinib FDA-approval date) were selected from the US-based PharMetrics® Integrated Database (2000–2011). Selected pts were required to be continuously eligible in their healthcare plan ≥6 months prior to and ≥30 days following trastuzumab or lapatinib initiation date. Pts were observed over the period spanning from trastuzumab or lapatinib initiation date (without restriction on line of therapy) up to the end of continuous health plan enrollment or data availability, whichever occurred first. Trastuzumab or lapatinib discontinuation rates (gap ≥45 consecutive days) were compared using multivariate Cox proportional-hazards models and reported as hazard ratios (HRs). Incremental HRU was estimated using negative binomial regression models and reported as incidence rate ratios (IRRs). Monthly cost difference (2010 USD; measured from a payer perspective) were estimated using multivariate generalized linear or two-part models. Since a large proportion of lapatinib users were previously treated with trastuzumab, a sensitivity analysis was conducted to control for the impact of prior trastuzumab use. Results: Among the 643 pts selected, 381 and 262 pts were initiated on trastuzumab and lapatinib, respectively. Of the 262 pts initiated on lapatinib, 171 (65%) were previously treated with trastuzumab. After adjustment for confounders (demographics, index year, prior MBC therapies, comorbidities, baseline HRU, and MBC duration), compared to trastuzumab users, lapatinib users had a higher rate of treatment discontinuation (HR = 1.57; p Sensitivity analyses showed that pts who were initiated on lapatinib without prior trastuzumab use had a higher incidence of inpatient admissions (IRR = 1.74; p = .002) and greater overall medical service costs compared to pts who were initiated on trastuzumab (adjusted difference=$3,059; p Conclusion: Overall, while MBC pts initiated on trastuzumab or lapatinib had similar healthcare costs, pts initiated on lapatinib had higher rates of treatment discontinuation and outpatient visits (not treatment administration related). Medical costs were significantly higher among pts initiated on lapatinib without prior trastuzumab use. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-18-12.


The aim of this article is to describe a classificatory framework, 'Land, body and spirit', which addresses the underlying causes of disease and which has proved useful in discussing with Northern Territory Aboriginal communities the causes and possible responses to premature adult deaths. Pie charts displaying proportional mortality ratios according to underlying cause of death, age and sex have also proved useful in such discussions.


The delivery of therapeutic agents is characterized by numerous challenges including poor absorption, low penetration in target tissues and non‐specific dissemination in organs, leading to toxicity or poor drug exposure. Several nanomedicine strategies have emerged as an advanced approach to enhance drug delivery and improve the treatment of several diseases. Numerous processes mediate the pharmacokinetics of nanoformulations, with the absorption, distribution, metabolism and elimination (ADME) being poorly understood and often differing substantially from traditional formulations. Understanding how nanoformulation composition and physicochemical properties influence drug distribution in the human body is of central importance when developing future treatment strategies. A helpful pharmacological tool to simulate the distribution of nanoformulations is represented by physiologically based pharmacokinetics (PBPK) modelling, which integrates system data describing a population of interest with drug/nanoparticle in vitro data through a mathematical description of ADME. The application of PBPK models for nanomedicine is in its infancy and characterized by several challenges. The integration of property–distribution relationships in PBPK models may benefit nanomedicine research, giving opportunities for innovative development of nanotechnologies. PBPK modelling has the potential to improve our understanding of the mechanisms underpinning nanoformulation disposition and allow for more rapid and accurate determination of their kinetics. This review provides an overview of the current knowledge of nanomedicine distribution and the use of PBPK modelling in the characterization of nanoformulations with optimal pharmacokinetics.


The objective of this study is to propose an effective method for measurement and analysis of fatigue crack. A technique that can measure the statue of fatigue crack propagation fast and correctly for enhancing safety of constructions and securing reliability is necessary. Moreover, the crack propagation behavior characteristics evaluation technique has to be developed using this technique. In this paper, fatigue crack was caused via the fatigue experiment with repeated load on the CT specimen that is made up of STS304. Fatigue crack propagation was measured by tracing the position of the maximum temperature according to the cycles using infrared thermography. The crack growth characteristics was evaluated by applying the moment values on the measuring area to the measured value. As a result of this study, the possibility that the infrared thermography could be applied to measure the fatigue crack was identified. Moreover, it was identified that fatigue crack propagation have a relationship with the moment value of construction.


The use of communication networks and intelligent electronic devices (IEDs) for power systems is becoming more common and more necessary. Changes in the power system structure, changes in requirements and the necessity to have easy access to accurate data have led to the need for communication systems. Due to these changes, communication systems with IEDs in power companies expose the safety-critical power companies' network to the multitude security problems of communication networks. This paper proposes a method called multiple channel secure acknowledging multicast, which merges the tasks of acknowledgment and key changes in a simple and direct manner to make exposed IEDs more secure in distribution automation.


The development of ICT has changed education through e-learning. Esa Unggul University has newly implemented e-learning, especially the department of Elementary Teacher Education. It aimed to investigate the factors influencing the implementation of e-learning for students of the Teacher Education Faculty. The case study method was implemented to conclude this research. The participants of this study were 50 students majoring in the department of Elementary Teacher Education. The data were gathered through e-questionnaire, LMS analysis, and document analysis. The result showed that the ITS infrastructures or LMS, Content Management, and Course Management were the component of e-learning that need to be improved.


PURPOSE
To determine if multi-detector row computed tomography (CT) can replace conventional radiography and be performed alone in severe trauma patients for the depiction of thoracolumbar spine fractures.

MATERIALS AND METHODS
One hundred consecutive severe trauma patients who underwent conventional radiography of the thoracolumbar spine as well as thoracoabdominal multi-detector row CT were prospectively identified. Conventional radiographs were reviewed independently by three radiologists and two orthopedic surgeons; CT images were reviewed by three radiologists. Reviewers were blinded both to one another's reviews and to the results of initial evaluation. Presence, location, and stability of fractures, as well as quality of reviewed images, were assessed. Statistical analysis was performed to determine sensitivity and interobserver agreement for each procedure, with results of clinical and radiologic follow-up as the standard of reference. The time to perform each examination and the radiation dose involved were evaluated. A resource cost analysis was performed.

RESULTS
Sixty-seven fractured vertebrae were diagnosed in 26 patients. Twelve patients had unstable spine fractures. Mean sensitivity and interobserver agreement, respectively, for detection of unstable fractures were 97.2% and 0.951 for multi-detector row CT and 33.3% and 0.368 for conventional radiography. The median times to perform a conventional radiographic and a multi-detector row CT examination, respectively, were 33 and 40 minutes. Effective radiation doses at conventional radiography of the spine and thoracoabdominal multi-detector row CT, respectively, were 6.36 mSv and 19.42 mSv. Multi-detector row CT enabled identification of 146 associated traumatic lesions. The costs of conventional radiography and multi-detector row CT, respectively, were 145 and 880 US dollars per patient.

CONCLUSION
Multi-detector row CT is a better examination for depicting spine fractures than conventional radiography. It can replace conventional radiography and be performed alone in patients who have sustained severe trauma.


Simultaneous Authentication of Equals (SAE) is a password-authenticated key exchange protocol that is designed to replace the WPA2-PSK-based authentication. The SAE authenticated key exchange protocol supports the peer-to-peer authentication and is one of the major authentication mechanisms of the Authentication and Key Management Suite specified within Wi-Fi. The SAE authenticated key exchange protocol has been widely implemented in today's Wi-Fi devices as part of major security feature upgrades and is regarded as the third generation of Wi-Fi Protected Access. This article presents a way of attacking the weaker randomness generation algorithm within the SAE protocols, which can lead to successful impersonation types of attacks. We also suggest some protocol amendments for protection. It is recommended that SAE implementations should be upgraded to ensure protection against these attacks.


The silhouette of a black hole having a critical curve (an unstable bound photon orbit) when illuminated by an optically thin accretion disk whose emission is confined to the equatorial plane shows a distinctive central brightness depression (the shadow) whose outer edge consists of a series of strongly lensed, self-similar rings superimposed with the disk's direct emission. While the size and shape of the critical curve depend only on the background geometry, the pattern of bright and dark regions (including the size and depth of the shadow itself) in the image is strongly influenced by the (astro)physics of the accretion disk. This aspect makes it difficult to extract clean and clear observational discriminators between the Kerr black hole and other compact objects. In the presence of a second critical curve, however, observational differences become apparent. In this work we shall consider some spherically symmetric black hole and wormhole geometries characterized by the presence of a second critical curve, via a uniparametric family of extensions of the Schwarzschild metric. By assuming three toy models of geometrically thin accretion disks, we show the presence of additional light rings in the intermediate region between the two critical curves. The observation of such rings could represent a compelling evidence for the existence of black hole mimickers having multiple critical curves.


The coral reefs and coral cornmunities in Golfo Dulce, southem Pacific Coast of Costa Rica, are described. The Inner Gulf reefs are characterized by a high topographic relief, low coral diversily and live coral covegage, and high dead coral coverage. The reefs can be zoned into: l . A reef-flat zone, where dead Pocillopora and Psammocora are predorninant, togetber witb live and dead rnicroatolls of Pori/es loba/a. 2. A reef-edge zone, where tbere is a marked change in physiognorny, from a relatively horizontal reef-flat to an a1rnost vertical reef-fronL Tbis is tbe zone witb highest live coral coverage and is for tbe most part Pori/es loba/a. 3. A reef-front, extending frorn 2 to 10 m deptb, made up mainly of dead Pori/es lobala. The Outer GuIf reeis are characterized by a low topograpbic relief, high live coral coverage and diversity, and low dead coral coverage. A total of nine sc1eractinian species were found in Golfo Dulce. Most abundant are PorIJes lobala, Psammocora stella/a and Pocillo poro damicornis, which have also becn present tbere tbroughout tbe Holocene. Twenty four fish species were observed in two reefs. Most of them are important for tbe artesanal fisheries of Golfo Dulce. Otber species are important recf herbivores or corallivores. Intemal ro- ral bioerosion (chief1y boring bivalves: Lithophaga) is more important tban extemal bioerosion. . Enviromnental conditions at Golfo Dulce were conducive to reef growth in the recent past but are now deteriorating as a result of inreased sediment loads. Deforestation, pemicioIls agricultural practices and miniog in tbe Golfo Dulce watershed must be brought under control and erosion reduced. H tbese were possible a program of reef rehabilitation by transplanting corals could be started to recover sorne of the reefs.


As indicated in this review, we have begun to elucidate cellular environments and trophic factors that promote the regeneration of adult mammalian CNS neurons. In the present paradigm, bilateral aspiration lesions of the fornix-fimbria are used to axotomize septal neurons and transect the septal cholinergic projection to the dorsal hippocampus in order to evaluate the influence of trophic factors, such as NGF, on neuronal survival and the ability of cellular transplants of PNS tissue to promote axonal regeneration in vivo. Initial results demonstrate that NGF is a potent trophic molecule that prevents retrograde degeneration of septal cholinergic neurons. Observations from transplantation studies demonstrate that viable Schwann cells obtained from PNS nerve grafts or Schwann cell-ECM cultures provide a favorable cellular milieu for CNS regeneration. These cellular transplants induce a remarkable sprouting response from septal cholinergic neurons and promote the rapid elongation of septal axons that reinnervate the denervated hippocampus. In stark contrast to the Schwann cell-laden transplants, transplants including only ECM channels synthesized by cultured Schwann cells do not promote axonal regeneration within the time periods that we have examined. Therefore, we hypothesize that viable Schwann cells are crucial for the process of regeneration because they contribute both trophic and tropic factors to the injured CNS neurons. The significant early sprouting phenomenon associated with transplants containing Schwann cells strongly suggests that soluble Schwann cell-synthesized factors induce axon elongation and possibly enhance the survival of injured septal neurons. The trophic factors probably function in a manner similar, if not identical, to the action of NGF on axotomized septal neurons. Moreover, Schwann cells appear to provide tropic signals, such as LAM or a LAM-NGF complex, that can act, when in the proper stereoconfiguration, to promote the elongation and orientation of regenerating axons. Thus, our current data indicate that in order to promote optimal axonal regeneration from injured CNS neurons, both trophic and tropic factors must be supplied from exogenous sources.


Background. Parkinson's disease (PD) is believed to develop from epigenetic modulation of gene expression through environmental factors that accounts for up to 85% of all PD cases. The main objective of this study was to examine the association between PD onset and a cumulative exposure to potentially modifiable ambient exposures. Methods. The study population comprised 3343 incident PD cases and 31,324 non-PD controls in Southern Israel. The exposures were determined based on the monitoring stations and averaged per year. Their association with PD was modeled using a distributed lag non-linear model and presented as an effect of exposure to the 75th percentile as compared to the 50th percentile of each pollutant, accumulated over the span of 5 years prior to the PD. Results. We recorded an adverse effect of particulate matter of size ≤10 μm in diameter (PM10) and solar radiation (SR) with odds ratio (OR) = 1.06 (95%CI: 1.02; 1.10) and 1.23 (95%CI: 1.08; 1.39), respectively. Ozone (O3) was also adversely linked to PD, although with a borderline significance, OR: 1.12 (95%CI: 0.99; 1.25). Immigrants arriving in Israel after 1989 appeared to be more vulnerable to exposure to O3 and SR. The dose response effect of SR, non-existent for Israeli-born (OR = 0.67, 95%CI: 0.40; 1.13), moderate for immigrants before 1989 (OR = 1.17, 95%CI: 0.98; 1.40) and relatively high for new immigrants (OR = 1.25, 95%CI: 1.25; 2.38) indicates an adaptation ability to SR. Conclusions. Our findings supported previous reports on adverse association of PD with exposure to PM10 and O3. Additionally, we revealed a link of Parkinson's Disease with SR that warrants an extensive analysis by research groups worldwide.


Talking of newspapers Charles Prestwick Scott said "At the peril of its soul it must see that the supply is not tainted. Neither in what it gives, nor in what it does not give, nor in the mode of presentation, must the unclouded face of truth suffer wrong. Comment is free but facts are sacred." The aim of this monograph is to adhere as closely as is possible to Mr Scott's opinion. As far as the facts of the proposed legislation are concerned, these will of course be untainted; the commentary which follows from these facts however, being free, proposes to examine and analyse the untainted factual supply.


The study examined the efficiency of resources used in soybean production in Kwara State using 120 representative farmers. The results of the descriptive statistics showed that 60% of the farmers had no former education with over 90% cultivating only a hectare of farm land to soybean. The costs and returns analysis revealed soybean production as a profitable enterprise with net farm income of N8,217.5 and rate of return of 62%. The regression results show labour in mandays, farm size in hectares and quantity of seeds in  kilogramme determined the production of soybean in the study area and should be the focus for policy targeting. Further analysis showed that land was underutilized while seeds and labour were over utilized. It was therefore recommended that more of land area should be utilized while less of quantities of labour and seeds should be used for optimal profit to be attained in the study area. Keyword s: Soybean production, efficiency measurement, profitability ratio analysis


In this article, we address the problem of multiple local optima arising due to nonconvex objective functions in cooperative multiagent optimization problems. To escape such local optima, we propose a systematic approach based on the concept of boosting functions. The underlying idea is to temporarily transform the gradient at a local optimum into a boosted gradient with a nonzero magnitude. We develop a distributed boosting scheme based on a gradient-based optimization algorithm using a novel optimal variable step size mechanism so as to guarantee convergence. Even though our motivation is based on the coverage control problem setting, our analysis applies to a broad class of multiagent problems. Simulation results are provided to compare the performance of different boosting functions families and to demonstrate the effectiveness of the boosting function approach in attaining improved (still generally local) optima.


Background: Intensive Care Unit Acquired Muscle Weakness (ICU-AW) is one of the most important complications occurs in the ICU. ICU-AW is a multifactorial syndrome characterized by generalized muscle weakness. Critical care nurses (CCNs) have an important role in the prevention of ICU-AW through increase mobility and applying of range of motion. Design: A descriptive exploratory design was utilized to achieve aim of this study. Aim: This study aimed to assess factors contributing to acquired muscle weakness among critical ill patients. Setting: the study was carried out in intensive care units of Beni–Suef University Hospital. Subjects: A Purposive sample of seventy five patients admitted in the previous mentioned setting. Tools of data collection were consisted of Patient assessment tool, muscle strength scale and indicators to incidence of ICU-AW and factors contributing to ICU-AW assessment tool. Results: revealed that more than half of the studied patients had ICU-AW. The majority of studied patients who had muscle weakness were older than the Non ICU-AW patients. Application of positioning and range of motion exercises were not done in the ICU-AW patients. Administration of corticosteroid and incidence of malnutrition was higher in the ICU-AW patients than the Non ICU-AW patients. There were no statistically significant relation between incidence of ICU-AW and gender, admission medical diagnosis, administration of parenteral nutrition and application of positioning and walking exercises. Conclusion: More than half of studied patients developed ICU-AW. The contributing factors of ICU-AW are patient age, WBCs level, not applying range of motion and chair sitting exercise to ICU patients, administration of corticosteroid and malnutrition. Recommendations: Further researches are recommended to study extensively the effect of nutritional status on incidence of ICU-AW. Also, examine the incidence of ICU-AW in sedated and unconscious patients.


Introduction: Allergic bronchopulmonary aspergillosis (ABPA) is an immunologic pulmonary disorder caused by a complex hypersensitivity response to inhaled fungal antigens. ABPA occurs most commonly in immunocompetent patients and complicates 1% to 2% of cases of persistent asthma and 7% to 14% of cases of chronic steroid-dependent asthma. Aim: The aim of this study was to study the clinical and radiological profile of patients and to study the serological correlation of ABPA. Methodology: This was a retrospective study done over 6 months from June 2020 to December 2020. Patients who were confirmed cases of ABPA according to the International Society for Human and Animal Mycology criteria were enrolled for the study. Patients' demographic data, pathological, and radiological test results were collected and analyzed. Pre- and post-bronchodilator spirometry of the patients were examined and asthma control was calculated. Results: In the present study, 23 patients were studied. Most patients were young, the mean age was 35.7 years with a female predominance of 56.5%. The most common symptom was cough in 91.3% of patients. All patients had bronchial asthma as a predisposing factor. The mean absolute eosinophil count and mean serum immunoglobulin E were 534 cells/μL and 2270 UI/ml, respectively. About 82.6% of participants in the study had spirometry suggestive of obstructive pattern. Bronchiectasis and parenchymal opacities were the most common radiological abnormality seen. Conclusion: The diagnosis of ABPA must be considered when treating difficult to control asthma. A delay in diagnosis can lead to decreased asthma control, worsening of lung function, sometimes leading to irreversible changes, poor quality of life, and increased cost of treatment.


Young's double slit experiments, which represent the mystery of quantum mechanics, have been described by either the classical wave, or quantum probability waves or pilot waves. Recently, the novel experiments show that the interference patterns of the double slit/cross-double slit experiments may be curved. The previous phenomena of the light bending contain the gravity bending and Airy beam curving transversely. The curved Airy beam is interpreted by the quantum Schrödinger's wave equation and electromagnetic wave theory. To study the curved interference patterns of the comprehensive double slit experiments, we study the underlying physics first, namely, to study whether the light beam/photons behave as wave or as particle before forming the curved interference pattern. In this article, the comprehensive double slit experiments are performed, which show: (1) the fringes of the curved interference pattern are created independently and may be create partially; (2) the longitudinal shield and the metal tube inserted between the slide and the detector has no effect on the interference pattern. The experimental observations suggest that, before forming the curved interference pattern on the detector, photons behave as particles, which can be referred as "wave-particle-coexistence". The phenomena provide the comprehensive information/data for the theoretical study.


Once a year, senior sales and marketing executives of many of America's largest companies gather at the Waldorf Astoria Hotel in New York City for the Conference Board's Annual Marketing Conference. Participants spend two days discussing evolving issues relating to the successful marketing of consumer and industrial goods and services. This paper is based on topics discussed at the Conference Board's November 2000 Annual Marketing Conference.
As the title indicates, the two primary foci of this conference in New York were ";marketing"; and e-business."; Of the two, it seems likely that the second is less well-known in Nigeria. Therefore, Part #1 of this paper overviews the different types (that is, a typology or taxonomy) of e-business models. Part #2 of the paper will consider a number of issues relating to the intersection of marketing on the one hand and the e-business environment on the other. Part #2 of the paper concludes with a short mini-case designed to stimulate readers' appreciation of the ways the issues raised could relate to a business in Nigeria.
(The Lagos Business School Management Review: 2002 7 (1): 1-43)


Because of the fast advancement in the creation of power electronics equipment such as automatic Machines, adjustable speed drives, personal computers and other non-linear loads which are the main sources of harmonics. Due to the presence of these nonlinear loads, it is necessary to reduce the level of harmonics created in the power networks. Hence, harmonic analysis of distribution networks is important. The analysis of power systems is an important part of power system engineering. Any electrical utility company's principal goal is to provide the best quality of power. The power system harmonics is one of the major reasons of poor power quality. Harmonics and harmonic analysis must be investigated in filters in order to minimize harmonic current and voltage. This paper aims to build a simulation model of nine bus ring system to evaluate characteristics of harmonics in different cases of study using Electrical Transient and Analysis Program (ETAP). Using ETAP harmonic distortion is analyzed and mitigation techniques are used represented by single tuned filters which should be installed for worst case and the best-case condition. And the simulation results of ETAP shows that some of THDv,i% results are within the limit value as per IEEE 519 -1992 standard.


Purpose: The purpose of this study was to validate the effects that the structured pamphlet and education through tablets regarding the daily life management and disease nursing education program has towards pneumonia patients in compliance, and self-efficacy.
Methods: This study used the quasi-experimental study design based upon the nonequivalent control group pretest-posttest design.
A total of 100 patients-50 patients who were hospitalized February 2020 as the control group and 50 patients who were hospitalized March 2020 as the experimental group – were used as material for the statistical analysis. These data were analyzed with a significance level of p<.05 using the SPSS WIN 21.0 program. Results: The patients' compliance, and self-efficacy had no significance difference between the two previous scores, meaning homogeneity in the two groups. Through verifying the experimental group who had disease and daily-life managing nursing education will have higher scores in compliance (t=20.95, p<.001), and self-efficacy (t=17.24, p<.001) than the control group who had not received those education, were statistically significantly different leading to all hypothesis being supported. Conclusion: For improving pneumonia patients' compliance, the methods should be simple, easy to understand, effective in numerous clinical situations, require constant education and reinforcement, and periodic nursing education program.


Location information is critical to a wide variety of navigation and tracking applications. GPS, today's de-facto outdoor localization system has been shown to be vulnerable to signal spoofing attacks. Inertial Navigation Systems (INS) are emerging as a popular complementary system, especially in road transportation systems as they enable improved navigation and tracking as well as offer resilience to wireless signals spoofing and jamming attacks. In this paper, we evaluate the security guarantees of INS-aided GPS tracking and navigation for road transportation systems. We consider an adversary required to travel from a source location to a destination and monitored by an INS-aided GPS system. The goal of the adversary is to travel to alternate locations without being detected. We develop and evaluate algorithms that achieve this goal, providing the adversary significant latitude. Our algorithms build a graph model for a given road network and enable us to derive potential destinations an attacker can reach without raising alarms even with the INS-aided GPS tracking and navigation system. The algorithms render the gyroscope and accelerometer sensors useless as they generate road trajectories indistinguishable from plausible paths (both in terms of turn angles and roads curvature). We also design, build and demonstrate that the magnetometer can be actively spoofed using a combination of carefully controlled coils. To experimentally demonstrate and evaluate the feasibility of the attack in real-world, we implement a first real-time integrated GPS/INS spoofer that accounts for traffic fluidity, congestion, lights, and dynamically generates corresponding spoofing signals. Furthermore, we evaluate our attack on ten different cities using driving traces and publicly available city plans. Our evaluations show that it is possible for an attacker to reach destinations that are as far as 30 km away from the actual destination without being detected. We also show that it is possible for the adversary to reach almost 60--80% of possible points within the target region in some cities. Such results are only a lower-bound, as an adversary can adjust our parameters to spend more resources (e.g., time) on the target source/destination than we did for our performance evaluations of thousands of paths. We propose countermeasures that limit an attacker's ability, without the need for any hardware modifications. Our system can be used as the foundation for countering such attacks, both detecting and recommending paths that are difficult to spoof.


Future wireless communication systems are characterized by heterogeneity in terms of node capabilities, link level requirements, propagation environments, cell designs and subnet structures. High carrier frequencies and large system bandwidth will make extreme diversity factors feasible. This imposes new requirements on space-time codes. We present a new concatenated linear space-time block coding scheme, which meets these requirements. The code consists of a linear time variant inner code and a linear time invariant outer code. We intentionally decouple the designs of each constituent code in order to achieve the required adaptivity. The inner code is optimized with respect to the variation of the instantaneous channel capacity over the block length of the outer code. Efficient inner coding matrices are given for pure TX diversity and joint spatial subchanneling and TX diversity. The linear outer code is optimized for diversity performance. We describe an efficient approach for the optimization of an unitary coding matrix for any given block length. Simulation results for different system parameters are presented. It is concluded that the proposed concatenated linear high rate space-time block coding scheme is a promising candidate for heterogeneous future mobile communication systems.


Abstract Impedance-controlled endometrial ablation (NovaSure) is commonly used to treat premenopausal heavy menstrual bleeding in Lothian, Scotland. Using postal questionnaires, we assessed patient satisfaction, treatment success and post-procedure symptoms in a cohort of women who had NovaSure treatment between January 2007 and May 2009. The response rate was 61.2% (115/188): 90.4% (104/115) of women were satisfied and would recommend the procedure; 36.8% (42/114) of women were amenorrhoeic at follow-up (mean = 497 days) and NovaSure significantly improved levels of both menstrual bleeding and pain (p < 0.01). Of the women, 67.0% (77/115) reported symptoms such as discomfort, vaginal discharge and bleeding/spotting within 6 weeks following NovaSure. A total of 13.9% (16/115) required further treatment following NovaSure, including hysterectomy. Patient satisfaction with NovaSure was high. Preoperative counselling needs to include information on character and duration of postoperative symptoms. Future research could compare patient satisfaction and clinical outcomes between NovaSure and the levonorgestrel-releasing intrauterine system.


A new method for measuring the sensitivity distribution of the picture element of the solid-state imager was proposed. The method can display the distribution on an oscilloscope, and high accuracy is attained by the optical system using a narrow-slit pattern and a high resolution projection lens. Theoretical analysis on the measurement error was also performed. The developed method will be an important tool for the precise evaluation of the resolution characteristics of the solid-state imager.


A NUMBER of diseases occur in man whose principle therapeutic requirement is supplementation of the diet with pyridoxine (vitamin B 6 ). A variety of interesting mechanisms underlie the need for this supplementation in the different disorders. This paper discusses these mechanisms and how some of them illustrate a new outlook on genetic modifications of biochemical reactions. Several forms of vitamin B 6 occur in biological systems; pyridoxal, pyridoxamine, and pyridoxine are found mainly in the extracellular fluid from where they may be readily transported intracellularly. 1 The most important intracellular forms of the vitamin are pyridoxal-5′-phosphate (PLP) (Figure), and pyridoxamine-5′-phosphate. All of the free forms are interchangeable and each can be phosphorylated; the latter forms are also interchangeable. Pyridoxal-5′-phosphate is degraded in the liver by oxidation to 4-pyridoxic acid (4-PA), which is then excreted in the urine. A series of specific enzymes effect these reactions. 3-5 Pyridoxal-5′-phosphate is the coenzyme


Despite a widely-acknowledged shortage of software developers, and reports of a gap between industry needs and software education, the possible gap between students' needs and software development education has not been explored in detail. In their university education, students want to take courses and carry out projects that clearly relate to their lives and their goals. This paper reports on a quantitative study of 297 software development students. The analysis of the results suggests that software development education has a predominantly social relevance to students and also has moderate personal and professional relevance. The following approaches are recommended to improve students' views of the relevance of software development education: use various learning environments; pay special attention to female students, students who did not have IT as a school subject, and students who rate their own academic performance as low; update educators on the latest developments; design programs to appeal to students and to meet societal demands.


2013 High-pressure (HP) metamorphic terrane in the Tongbai orogen comprises two HP slices (I and II) and a tectonic mélange zone in the northeast and a blueschist-greenschist zone in the southwest. HP slice I is represented by the northern and southern eclogite zones on the two sides of the Tongbaishan antiform. HP slice II is represented by retrograded eclogite-bearing metamorphic enclaves in Cretaceous gneissic granites in the Tongbai Complex. U-Pb, Lu-Hf, Rb-Sr and 40 Ar/ 39 Ar multichronometric data indi-cate that the peak metamorphism of HP slice I took place at ~255 Ma, whereas the metamorphic ages of HP slice II are as young as 232–220 Ma. By contrast, the tectonic mélange zone near the suture was metamorphosed at ~256 Ma. Such a diachroneity of different slices across the direction of the orogen in the Hong'an-Dabie-Sulu HP/UHP terrane is ubiquitous, and it can be interpreted by a syn-subduction detachment/exhumation model. Furthermore, the metamorphic age of HP slice I in the Tongbai orogen is older than that of the equivalent HP slice in the Hong'an orogen by ~15 Ma, suggesting that the diachroneity may have also existed along the direction of the orogen. A seesaw-type subduction/exhumation model is proposed to explain this age disparity and the subduction of the South China Block becomimg shallower towards the


The present paper discusses types of management uncertainty exemplified by the case study of a project of building a multifunctional harbor transshipping center. The analysis is based on the ideas and works of I. Fischer. The paper shows that the role of project management actors substantially influences risks and that change of the actor's role leads to minimization of risks and elimination of uncertainty about project realization time. To analyze project risks the authors develop a complex model of risk assessment based on analysis of probability and impact level of undesired events. Probability of undesired events is presented as a matrix of risk ranks and a tool for analyzing project risks based on the matrix of risk ranks and FMEA analysis is developed.


The relationship between domain-general and domain-specific creative thinking ability was examined in 3 studies using structural equation modeling. Learning disability, ethnicity, gender, and age/grade were included in the model to test their differential effects on general and specific creative thinking. In Study 1 (N = 130), learning disability, grade (high school, college), and gender were included in the model in addition to the 2 latent variables (general and specific creative thinking ability). In Study 2, with elementary students (N = 108), ethnicity, grade (4th, 5th, and 6th graders), and gender were included. In Study 3, with preschool children (N = 71), age and gender were included. In all 3 studies, domain-general and domain-specific creative thinking ability were found to be distinguishable yet related, and the former had a causal effect on the latter. Age/grade level, gender, ethnicity, and learning disability status discriminated the 2 constructs—general and specific creative thinking ability. We concluded that different life experiences (schooling and culture) may have stronger impacts on domain-specific creative thinking than domain-general creative thinking.


Basal ganglia dysfunction causes profound movement disorders, often attributed to imbalance between direct and indirect pathway activity in the sensorimotor basal ganglia. In the classical view, the direct pathway facilitates movements, whereas the indirect pathway inhibits movements. However, the recent finding of co-activation of the two pathways during movement challenges this view. Reconciling the new finding with the body of evidence supporting the classical view, this perspective proposes that the direct pathway computes the expected benefits of motor plans entering the basal ganglia, while the indirect pathway computes their expected costs. Thus, basal ganglia output combining the two pathway signals in a subtraction manner weighs benefits against costs, and endorses the plan with the best prospective outcome via feedback projections to the cortex. The cost-benefit model, while retaining the antagonistic roles of the two pathways for movements, requires co-activation of the two pathways during movement as both benefit and cost are computed for every movement. The cost-benefit model, though simple, accounts for a number of confounding results, and generates new focus for future research with testable predictions.


Helicobacter pylori is a Gram-negative bacteria that is responsible for gastritis in human. Its spiral flagellated body helps in locomotion and colonization in the host environment. It is capable of living in the highly acidic environment of the stomach with the help of acid adaptive genes. The genome of H. pylori 26695 strain contains 1,555 coding genes that encode 1,445 proteins. Out of these, 340 proteins are characterized as hypothetical proteins (HP). This study involves extensive analysis of the HPs using an established pipeline which comprises various bioinformatics tools and databases to find out probable functions of the HPs and identification of virulence factors. After extensive analysis of all the 340 HPs, we found that 104 HPs are showing characteristic similarities with the proteins with known functions. Thus, on the basis of such similarities, we assigned probable functions to 104 HPs with high confidence and precision. All the predicted HPs contain representative members of diverse functional classes of proteins such as enzymes, transporters, binding proteins, regulatory proteins, proteins involved in cellular processes and other proteins with miscellaneous functions. Therefore, we classified 104 HPs into aforementioned functional groups. During the virulence factors analysis of the HPs, we found 11 HPs are showing significant virulence. The identification of virulence proteins with the help their predicted functions may pave the way for drug target estimation and development of effective drug to counter the activity of that protein.


Theobjectiveof the study was to detect the frequency and sources of hemorrhagic complications in patients with pancreatitis, evaluate the tactics and effectiveness of methods of hemostasis.Material and methods.A retrospective analysis of hemorrhagic complications of pancreatitis was carried out in 40 patients.Results.Bleeding developed mainly on the background of infected acute necrotic collections (77.8 %), the main source of bleeding was the splenic artery (37.0 %). Emergency laparotomy for bleeding was performed in 9 (22.5 %) patients, selective angiography was performed in 10 patients, it was effective only in 5 (50 %) cases. 12 (44.4 %) deaths were recorded in cases of arrosive bleeding.Conclusion.The preferred tactics in case of bleeding from the retroperitoneal space during minimally invasive treatment is crossclamping of drains and endovascular hemostasis.


Abstract Anorexia nervosa (AN) has been associated with weaknesses in central coherence and set shifting. In this line, it has been proposed to directly address these neuropsychological features in treatment (e.g., cognitive remediation therapy). It is not clear, however, whether the 2 subtypes of AN, the restricting (AN-R) and bingeing/purging (AN-BP) type, have the same amount of problems in these domains. A systematic search of the literature was conducted, using the databases Web of Science and PubMed, looking for studies on the comparison of AN-R and AN-BP in performing central coherence/set-shifting tasks. Notably, very few authors describe the results of a direct comparison of the performance of patients with AN-R and AN-BP. In summary, the available indications for possible group differences are not strong enough to draw definitive conclusions.


With the start of the LHC, the new particle collider at CERN, the ATLAS experiment is also providing high-energy particle collisions for educational purposes. Several education projects—education scenarios—have been developed and tested on students and teachers in several European countries within the Learning with ATLAS@CERN project. These highly appreciated projects could become a new component in many teachers' classrooms. The Learning with ATLAS portal and the information on the ATLAS public website make it possible for teachers to design educational material for their own situations. To be able to work with real data adds a new dimension to particle physics explorations at school.


The alpha 4 integrins mediate leukocyte adhesion to specific counter-receptors, including vascular cell adhesion molecule-1 (VCAM-1), the fibronectin splice variant containing connecting segment 1 (CS1), and mucosal addressin cell adhesion molecule-1. A series of cyclized peptides based on the LDV sequence of CS1 were synthesized and assayed for inhibition of alpha 4 integrin binding. The most potent peptide, C*WLDVC* (where * indicates disulfide-linked residues), inhibited alpha 4 beta 1-dependent binding of lymphocytes to VCAM-1 and CS1 with half-maximal inhibition achieved at 1 to 3 microM of peptide. The peptide proved more potent when the lymphocytes were activated with 1 mM MnCl2; half-maximal inhibition was reached at 0.4 and 0.05 microM for VCAM-1 and CS1, respectively. This represents a 100- to 800-fold increase in potency over a linear CS1 peptide in these same assays. C*WLDVC* also inhibited alpha 4 beta 7-dependent lymphocyte binding to the ligands mucosal addressin cell adhesion molecule-1, VCAM-1 and CS1. Immunoprecipitation of radiolabeled integrin indicated that the peptide could bind alpha 4 beta 1 and alpha 4 beta 7 directly and elute alpha 4 beta 1 from a CS1-conjugated agarose resin. The peptide showed selectivity for alpha 4 integrins in that it effectively inhibited alpha 4 beta 1-dependent, but not alpha 5 beta 1-dependent, binding of cells to intact fibronectin. Due to its small size and potency, C*WLDVC* may serve as a useful tool for the study of alpha 4 integrin biology and the development of small molecule therapeutics.


The full energy shift of a massive Dirac neutrino in magnetized electron-positron plasma was investigated using the Matsubara imaginary time and real time formalisms. The neutrino dispersion in the magnetized medium was analyzed as a function of the neutrino spin and mass. It was shown that in a super-strong magnetic field the СP-symmetric plasma contribution to the neutrino energy greatly exceeds the analogous correction in the field-free case. The contribution of plasma to the anomalous magnetic moment of a neutrino was obtained.


In this paper, the performance of similarity retrieval from satellite image databases by using different sets of spatial and transformed-based texture features is evaluated and compared. A benchmark consisting of 37 satellite image clips from various satellite instruments is devised for the experiments. We show that although the proposed feature set perform only slightly better with the Brodatz set, its performance is far superior for the satellite images. The result indicates that more than 25% of the benchmark patterns can be retrieved with more than 80% accuracy by using normalized Euclidean distance. In contrast, less than 10% of the patterns are retrieved with more than 80% accuracy by using transformed-based feature sets (such as those based on Gabor filter or quadrature mirror filter (QMF)).


The fundamental assumption in the management of predators is that reducing predator numbers will reduce their predation impact on livestock. Research on dingoes (Canis lupus dingo) has shown this assumption to be incorrect in beef production areas in northern and western Queensland. Aerial and ground baiting with 1080 (fluoroacetate) is the principal dingo-control method used in extensive pastoral areas of Australia. This paper compares four approaches to measure the effectiveness of these control programs. Dingo abundance was reduced in 11 of 13 baiting campaigns monitored with almost two-thirds of these producing > 50 % reduction. However, concurrent decline in dingo abundance occurred in non-baited areas due to seasonal changes in dingo populations. When this was taken into account, less than half of the control programs produced >50% reduction. The time taken for dingoes to recolonize baited areas is also an important measure of effectiveness. In two-thirds of the control programs, conducted in the first nine months of the year, dingoes recolonized prior to the period of peak calving (November/December) when the biggest threat to calves existed. The timing and the scale of control programs affect the rate of re-colonization. Calf loss was subsequently higher and occurred more frequently in baited areas compared to non-baited areas. Seasonal conditions, the status of prey populations and the impact of control programs on social organization and prey selection, are key factors affecting calf predation. Control programs should be assessed by measuring impact rather than changes in predator numbers. The assumption that a direct relationship exists between predator numbers and impact is not valid for dingoes in beef production areas in northern Australia.


Abstract Background The present article describes two cases of patients with coronary arteritis (CA) whose identification of CA diagnosis (late vs. early) resulted in different clinical courses and outcomes. Case summary Case 1 is a 53-year-old woman with multiple coronary risk factors who was admitted with acute coronary syndrome (ACS) and significant stenosis in the left main trunk (LMT). Although clues suggested arteritis (LMT lesion without any other stenosis, occlusion of left internal thoracic artery, etc.), the diagnosis of CA (coronary involvement of unclassified arteritis) was delayed and revascularization, including coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI), was performed under uncontrolled inflammatory status. As a result, Case 1 experienced repeated ACS episodes due to graft failure and in-stent restenosis, and repeatedly underwent PCI. Case 2 is a 76-year-old woman with no significant coronary risk factors who was admitted with ACS. This patient was successfully diagnosed with coronary involvement of Takayasu arteritis before revascularization. Coronary artery bypass grafting was performed after stabilizing inflammation with prednisolone, and the patient remains angina-free beyond 1-year post-CABG. In both cases, intravascular imaging clearly identified the localization and degree of inflammation related to CA by demonstrating specific findings (ambiguous typical three-layer structure of arterial wall and extended low-echoic areas within adventitia). Discussion Accurate and early diagnosis with meticulous diagnostic and therapeutic strategies appear to be important for favourable clinical outcomes in the medical treatment of patients with coronary involvement of arteritis. Intravascular imaging has the potential to contribute to optimizing clinical management of CA.


Phenylalanine ammonia lyase was characterized in roots of Pinus sylvestris L. The Km for the pine root enzyme with phenylalanine as a substrate was l.2 ± 0.4 X 10-4 M. The enzyme had a pH activity optimum of 9 and the subunit molecular weight was 70 to 72 kD as determined by Western blotting. Enzyme activity could be inhibited by D,L-2-aminooxy 3 phenylpropionic acid at 1 μ. Treatments with zymosan, pectinase, light or kinetin and naphthylacetic acid did not induce higher phenylalanine ammonia lyase or peroxidase activity in pine roots. No significant differences were observed in phenylalanine ammonia lyase or peroxidase activity in mycorrhizal and nonmycorrhizal short roots in the P. sylvestris-L. laccata symbiosis 15 weeks after cultivation.


We apply first principles computational techniques to analyze the two-electron, multistep, electrochemical reduction of CO(2) to CO in water using cobalt porphyrin as a catalyst. Density functional theory calculations with hybrid functionals and dielectric continuum solvation are used to determine the steps at which electrons are added. This information is corroborated with ab initio molecular dynamics simulations in an explicit aqueous environment which reveal the critical role of water in stabilizing a key intermediate formed by CO(2) bound to cobalt. By use of potential of mean force calculations, the intermediate is found to spontaneously accept a proton to form a carboxylate acid group at pH < 9.0, and the subsequent cleavage of a C-OH bond to form CO is exothermic and associated with a small free energy barrier. These predictions suggest that the proposed reaction mechanism is viable if electron transfer to the catalyst is sufficiently fast. The variation in cobalt ion charge and spin states during bond breaking, DFT+U treatment of cobalt 3d orbitals, and the need for computing electrochemical potentials are emphasized.


Insulin resistance, a risk factor for cardiovascular disease, is increasingly seen in persons infected with HIV. In those affected, it is unclear whether insulin resistance is a direct result of HIV infection alone; however, the development of insulin resistance has been established as a complication of antiretroviral therapies. Some protease inhibitors (PIs) are culpable, and there are significant differences in the impact of different PIs on glucose metabolism, with current evidence suggesting that atazanavir does not cause insulin resistance. The paucity of standardized laboratory tests makes early diagnosis of insulin resistance relatively elusive. Still, there are some clinically useful methods for assessing its presence. For prevention and/or treatment, exercise and optimal diet are useful, and metformin and rosiglitazone have been shown to improve insulin resistance. Changing an effective antiretroviral regimen to counter insulin resistance must be approached thoughtfully in carefully selected patients.


COVID-19 has been declared as global epidemic and currently there is no drug/vaccine available to treat COVID-19. All over the world, several studies are being conducted to discover the antiviral drugs against COVI-19. Traditional medicinal plants have long history to treat viral infections. We adopted in silico approach to find out if unique phytocompounds such as emodin (Rheum emodi), thymol and carvacrol (Thymus serpyllum) and artemisnin (Artemisia annua) could physically bind COVID-19 target proteins such as SARS-CoV-2 spike glycoprotein (PDB ID: 6VXX), SARS-CoV-2 spike ectodomain structure (PDB ID: 6VYB), and SARS coronavirus spike receptor-binding domain (PDB ID: 2AJF) and in turn preventCOVID-19 binding to the host receptor ACE2. Since Chloroquine (a standard antimalarial drug) has been looked as potential therapy against COVID-19, we also compared the binding of chloroquine and plant origin artemisnin antimalarial drug for its interaction with 6VXX, 6VY and 2AJF. Molecular docking studies using AutoDock/Vina software revealed that among all the phytocompounds artemisinin showed best binding affinity with 6VXX, 6VYB and 2AJF with Etotal -10.5 KJ mol-1, -10.3 KJ mol-1, and -9.1 KJ mol-1 respectively. Whereas emodin, carvacrol and thymol binds with 6VXX, 6VYB and 2AJF with Etotal -6.4, -6.8, -6.9 KJ mol-1, -8.8, -6.8, -7.4 KJ mol-1, and -6.9, -7.4, -7.2 respectively. Similarly, with Autodock/Vina chloroquine showed less binding affinity with 6VXX (-5.6 KJ mol-1), 6VYB (-5.9 KJ mol-1) and 2AJF (-6.4 KJ mol-1) as compared to all phytocompounds. Toxicity prediction showed non-toxicity and non-carcinogen by admetSAR and PROTOX‑II software.


Ubiquitination is a post-translational modification involving the reversible attachment of the small protein ubiquitin to a target protein. Ubiquitination is involved in numerous cellular processes, including the membrane trafficking of cargo proteins. However, the ubiquitination of the trafficking machinery components and their involvement in environmental responses are not well understood. Here, we report that the Arabidopsis thaliana trans-Golgi network/early endosome (TGN/EE) localized SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) protein SYP61 interacts with the transmembrane ubiquitin ligase ATL31, a key regulator of resistance to disrupted carbon (C)/nitrogen/(N)-nutrient conditions. SYP61 is a key component of membrane trafficking in Arabidopsis. The subcellular localization of ATL31 was disrupted in knockdown mutants of SYP61, and the insensitivity of ATL31-overexpressing plants to high C/low N-stress was repressed in these mutants, suggesting that SYP61 and ATL31 cooperatively function in plant responses to nutrient stress. SYP61 is ubiquitinated in plants, and its ubiquitination level is upregulated under low C/high N-nutrient conditions. These findings provide important insights into the ubiquitin signaling and membrane trafficking machinery in plants.


The secondary structure of a staphylokinase variant (K35R, DGR) encapsulated in poly (lactic-co-glycolic acid) (PLGA) microspheres was quantitatively examined by Fourier transform infrared (FTIR) spectroscopy. Resolution enhancement technique and Fourier deconvolution were combined with band with curve-fitting procedures to quantitate the spectral information from the amide I bands. Nine component bands were found under the broad, nearly featureless amide I bands and assigned to alpha-helix, beta-sheet, turn and irregular (random) structures. The changes of bands at 1 651 and 1 623 cm(-1) after encapsulation were discussed.


The renewal energy technologies are increasingly popular to ensure future energy sustenance and address environmental issues. The tides are enormous and consistent untapped resource of renewable energy. The growing interest in exploring tidal energy has compelling reasons such as security and diversity of supply, intermittent but predictable and limited social and environmental impacts. The tidal energy industry is undergoing an increasing shift towards diffuser augmented turbines. The reason is the higher power output of diffuser augmented turbines compared to conventional open turbines. The purpose of this study is to present a comprehensive review of diffuser augmented horizontal axis tidal current turbines. The components, relative advantages, limitations and design parameters of diffuser augmented horizontal axis tidal current turbines are presented in detail. CFD simulation of NACA 0016 airfoil is carried out to explore its potential for designing a diffuser. The core issues associated with diffuser augmented horizontal axis tidal current turbines are also discussed.


Long overpromised and underdelivered, gene therapy has at last achieved clinical validation and, with the advent of improved gene editing technologies such as CRISPR, seems poised to play a rapidly expanding role in medical care. However, some of the intrinsic qualities of gene therapy pose a unique challenge to our health insurance model. Gene therapy is costly for a number of reasons. It is "personalized medicine," which means that treatments are individualized and not for a broad audience. Additionally, the goal of gene therapy is to provide a one-time cure, so the cost is upfront and not spread over time as it would be with conventional drugs or therapeutics. As our experience to date illustrates, these issues of cost may adversely affect access. In this Article, we argue that a lack of broad access to gene therapy will deepen existing health inequities and may create a society of genetic haves and have-nots, where certain genetic diseases become something that happens only to those who cannot afford treatment. This in turn may increase stigma and decrease resources for affected individuals. For these reasons, the success of gene therapy must be considered as inextricable from issues of cost and coverage.


Abstract The medium-sized historical towns in Czechia have at their disposal a preserved cultural heritage which constitutes important potential for tourism. Apart from some exceptions, these towns are rarely a destination of tourists, but rather of the visitors who come to visit them in connection with a targeted stay destination. They also choose them as an alternative to optional excursions, just from the destination of their stay (also from the place of their permanent residence). Based on the intensification indicators calculated from publicly accessible data, this study answers the question of what the position of tourism in the selected towns (Czech royal towns with the population size between 10,000 and 30,000 inhabitants) is. Based on the strategic documents, it analyses what strategies were chosen by the selected royal towns for their development. It also analyses whether the topic of tourism that can undoubtedly without doubts rely on its historical potential, declared by legislative protection of cultural heritage, is represented and what its importance is.


Indoleamine 2,3-dioxygenase (IDO) is an enzyme that catabolizes the amino acid tryptophan, leading to inhibition of T lymphocyte proliferation, whether by depletion of this amino acid in the environment, or by induction via the catabolites inducing apoptosis. In mammals, this enzyme acts on various conditions of the body such as pregnancy, infections, chronic inflammation, transplantation and tumors, acting in immune regulation. Recent studies have identified the presence of homologous molecules IDO lower phylogenetically related species, whose function appears to be confined to the tryptophan metabolism as an energy source. This study aimed to investigate the expression of IDO in blood cells and hematopoietic organs of rainbow trout by immunohistochemistry, seeking evidence that it could, this species is related to the immune system. The expression of IDO was observed in hematopoietic organs studied including head kidney that show labeling in interrenal cells and leukocytes; spleen, in which the marking restricted to a few leukocytes in the liver;, labeling was restricted to only certain cells within the blood vessels and the blood extensions can view the marking of some leukocytes including monocytes, lymphocytes and neutrophils. The predominance of IDO marking these tissues may constitute evidence that IDO identified in O. mykiss is related to the immune system in this species.


Vesicular traffic within the early secretory pathway is mediated by COPI- and COPII-coated vesicles. While COPII-coated vesicles appear to be involved exclusively in the export of secretory proteins and lipids from the endoplasmic reticulum (ER), COPI-coated vesicles seem to function in both anterograde and retrograde transport between the ER-Golgi intermediate compartment (IC) and the Golgi as well as in intra-Golgi transport. Here, we focus on (i) the mechanisms how these transport carriers are formed from a given donor membrane; and (ii) the possible mechanisms involved in sorting of proteins and lipids into such transport vesicles.


Reasoning may help solving problems and understanding personal experiences. Ruminative reasoning, however, is inconclusive, repetitive, and usually regards negative thoughts. We asked how reasoning as manifested in oral autobiographical narratives might differ when it is ruminative versus when it is adaptive by comparing two constructs from the fields of psychotherapy research and narrative research that are potentially beneficial: innovative moments (IMs) and autobiographical reasoning (AR). IMs captures statements in that elaborate on changes regarding an earlier personal previous problem of the narrator, and AR capture the connecting of past events with other parts of the narrator's life or enduring aspects of the narrator. A total of N = 94 university students had been selected from 492 students to differ maximally on trait rumination and trait adaptive reflection, and were grouped as ruminators (N = 38), reflectors (N = 37), and a group with little ruminative and reflective tendencies ("unconcerned," N = 19). Participants narrated three negative personal experiences (disappointing oneself, harming someone, and being rejected) and two self-related experiences of more mixed valence (turning point and lesson learnt). Reflectors used more IMs and more negative than positive autobiographical arguments (AAs), but not more overall AAs than ruminators. Group differences were not moderated by the valence of memories, and groups did not differ in the positive effect of narrating on mood. Trait depression/anxiety was predicted negatively by IMs and positively by AAs. Thus, IMs are typical for reflectors but not ruminators, whereas the construct of AR appears to capture reasoning processes irrespective of their ruminative versus adaptive uses.


Atmospheric plasma spraying is used to deposit alumina and alumina-graphite composite coatings. The influence of arc current (plasma temperature) on the microstructure, roughness, elemental composition, and phase composition of the coatings is analyzed by scanning electron microscopy (SEM), surface roughness testing, energy dispersive X-ray spectroscopy (EDX), and X-ray diffraction (XRD). The tribological properties of the sprayed coatings are analyzed using a tribometer with a ball-on-flat configuration. The roughness of the as-sprayed coatings increases and the size of the granules decreases with the increase in plasma temperature. The results demonstrate that the friction coefficients and wear rates are slightly reduced for Al2O3 coatings sprayed at higher arc currents. The Al2O3-graphite coatings register lower friction coefficient values than the Al2O3 coatings under dry sliding conditions.


The thesis goal is to improve the I/O performance of the PiSVM suite of parallel and scalable tools used for machine learning on HPC platforms. This is achieved by analyzing the current state of I/O and then designing an I/O framework that enables PiSVM programs to read and write data in parallel, using the HDF5 library. HDF5 is a highly scalable library that is used in HPC but its use is not widespread. The thesis implements the design into the PiSVM toolset as a proof-of-concept. A parser will be added to the PiSVM suite that converts data from the currently used SVMLight format into HDF5 format. A 3.45% overall reduction in execution time was achieved in PiSVM-Train on the Indian Pines Raw dataset. A 4.88% overall reduction in execution time was achieved in PiSVM-Predict on the Indian Pines Raw dataset. Read and write times were improved by a bigger percentage, upward to 98% reduction in read and write times. This can be attributed to the design of the I/O framework and usage of advanced data storage features that HDF5 o ers. A further signi cant result is a reduction of data le size by 72% and a reduction of model le size by 24% on the Indian Pines Raw dataset. In practice, any work with PiSVM will gain signi cant bene ts from the work done in this thesis. Whole research groups tend to have multiple copies of the data, working with di erent feature engineering techniques and As PiSVM is used in many supercomputing centers and by multiple research groups, the gains are signi cant.


Did religion promote or discourage participation in protest against authoritarian regimes during the Arab Spring? Using unique data collected in Tunisia and Egypt soon after the fall of their respective regimes, we examine how various dimensions of religiosity were associated with higher or lower levels of protest during these important events. Using these original new data, we reach a novel conclusion: Qur'an reading, not mosque attendance, is robustly associated with a considerable increase in the likelihood of participating in protest. Furthermore, this relationship is not simply a function of support for political Islam. Evidence suggests that motivation mechanisms rather than political resources are the reason behind this result. Qur'an readers are more sensitive to inequities and more supportive of democracy than are nonreaders. These findings suggest a powerful new set of mechanisms by which religion may, in fact, help to structure political protest more generally.


The application of genetics for the management of natural resources is expanding, and within this field, DNA registers will play an increasing role. The Norwegian minke whale DNA register, established in 1996, was designed primarily as a control system to detect any attempts at illegal trade of products derived from other stocks of minke whale, or other whale species, under cover of the legal Norwegian harvest originating from the Northeast Atlantic. The register contains genetic data for 7644 of 7751 whales landed in the period 1997–2010. Profiles are established from sequencing part of the mtDNA control region, analysis of 10 STRs and a sex-determining marker. Probabilities of genotypes matching between two randomly selected whales are 6.0−04 and 3.0−08 for five and eight of the STR loci, respectively. This permits verification of traded whale products via match to the register. The register has also been used in a number of ad hoc scientific studies resulting through the accumulation of genetic, demographic and biological data. Here, we review the register's logistics, specifications and evaluate the potential to apply similar registers to control the exploitation of other marine species.


Polarimetry has been recognized as a very important observational parameter for high energy astrophysics (>; 100 keV). For this reason the capability to perform accurate polarimetric measurement of high energy cosmic sources should be included in future space mission proposals. This idea has become very appealing in the perspective of new high energy focusing telescope implementing Laue lenses. In order to optimize the focal plane design of such mission as a Compton scattering gamma-ray polarimeter, a CdZnTe detector prototype has been tested at the ESRF (European Synchrotron Radiation Facility) under a ~ 100% polarized gamma-ray beam. The prototype detector tested is a 5 mm thick CdZnTe array with the anode segmented into 16 × 16 pixels of 2.5×2.5 mm2. One of the most important factors that can affect significantly the polarimetric measurements is the direction of the incoming photons from the polarized radiation source with respect to the focal plane of the polarimeter. We have studied and analyzed the polarimetric response of the CdZnTe prototype as a function of the inclination of a polarized beam with respect to the optical axis of the detector from 0° to 10° tilt angle.


Background Cystic fibrosis (CF) remains an incurable condition in respiratory medicine. One of the main symptoms is dyspnoea. CF is a multi-system disorder and treatment of pulmonary symptoms tends to focus on medication which can be nebulised therefore minimizing the systemic side effects. Traditionally in palliative medicine opioids are effective at relieving dyspnoea however nebulised opioid is not routinely recommended. In patients with CF who are at risk of gastrointestinal complications such a distal intestinal obstruction syndrome(DIOS), administration of nebulised opioids has been sporadically reported to improve dyspnoea and minimize the risk of constipation. The aim of this systematic review was to examine the role of nebulised opioids in improving dyspnoea in patients with CF. Methods Medline (1946–2018) and Embase (1974–2018) were searched. Eligible studies met the following criteria: patients with CF, patients>13 years of age Results 70 studies were eligible. Three studies fulfilled the criteria for review. The three studies described different case reports of nebulised opioid in patients with CF. The ages ranged from 13 years to 48 years. All patients had end stage respiratory failure due to CF. Two patients received nebulised morphine and one patient received nebulised fentanyl. Improvements in dyspnoea were graded according to improvement in BORG score. An adverse effect of a headache was noted in one patient occurring 48 hours after nebulised morphine had commenced. Conclusion Nebulised morphine and fentanyl have been used to improve dyspnoea due to CF in a very limited number of patients, therefore no conclusion advocating the use of nebulised opioids can be made. Further research in the form of randomised controlled trials is needed to improve the evidence base of symptom control in patients with CF. This research must also focus on adverse gastrointestinal side effects such as constipation increasing the risk of DIOS.


Studies have shown the overexpression of metastasis-associated protein 2 (MTA2) to be associated with hepatocellular carcinoma (HCC) progression. However, the molecular mechanism of MTA2 expression in HCC is unclear. In our study, we found a higher level of MTA2 in HCC tissues than in normal tissues and a significant correlation between tumor grade and overall survival of HCC patients. We also found that MTA2 inhibition reduced the migration and invasion capabilities of HCC cells, independent of cell proliferation. Mechanistic studies have suggested that MTA2 protein and mRNA are more highly expressed in SK-Hep-1 and Huh-7 cells compared with other HCC cells. MTA2 silencing drastically reduced migration and invasion capability and also inhibited matrix metalloproteinase 2 (MMP2) at the transcriptional and translation levels in both cells. In addition, treatment with the MMP2 antibody markedly impaired MTA2-knockdown-mediated inhibition of migration and invasion in SK-Hep-1 cells. Furthermore, MTA2 knockdown reduced the phosphorylation of the p38MAPK protein, whereas the inhibition of p38MAPK (SB203580 or si-p38) confirmed that blocking the p38MAPK pathway mediated MTA2-knockdown-inhibited migration and invasion in SK-Hep-1 cells. We demonstrated the molecular mechanism by which MTA2 inhibits human HCC cell metastasis through the p38MAPK/MMP2 pathways, which might be helpful in determining the diagnostic value of this protein in patients with HCC


Type 2 diabetes mellitus (T2DM) and prediabetes (or patients at risk for diabetes) have been increasing in epidemic proportions. Dyslipidemia and hypertension are cardiovascular risk factors frequently associated with diabetes and prediabetes. Bile acid sequestrants (BAS) were initially approved for the treatment of elevated low-density lipoprotein cholesterol (LDL-C), but they were subsequently found to have a glucose-lowering effect as well. Colesevelam hydrochloride (HCl), a BAS, has been approved as an adjunct to diet and exercise to improve glycemic control in adults with T2DM based on several studies that used it as an addition to sulfonylurea-based, metformin-based, and insulin-based therapies. Colesevelam HCl has not been approved for use for glycemic control in type 1 diabetes or for treating diabetic ketoacidosis and has not been studied in T2DM as monotherapy or in combination with dipeptidyl peptidase 4 inhibitors, or extensively with thiazolidinediones. A recent study has examined the combination of colesevelam HCl and metformin as an initial therapy for treatment-naïve patients with T2DM. Another recent study, which looked at colesevelam for the treatment of dyslipidemia of prediabetes, raised the possibility of the use of colesevelam therapy for both dyslipidemia and hyperglycemia of T2DM. This article reviews and summarizes the recent clinical studies regarding colesevelam as therapy for both diabetes and dyslipidemia. This dual mechanism of action is an attractive feature for the treatment of diabetes.


This paper presents a description of the architecture NOMOHi (Node, Mobile, Hybrid, Intelligent), which combines devices capable of communicating simultaneously and collaboratively on two or more radio communications technologies, supporting processes of artificial intelligence for it. It establishing a classification and ranking is based capabilities and radio communications services. A physical architecture is recommended by 5 layers of abstraction that can be changed and updated without affecting the communications interoperability and 6 layers for the Security Architecture. It specially describes the characteristics of sensor devices NOMOHi 802.11/Bluetooth/UWB and the WiMAX 802.16e/802.11 network services, and its potential practical applications for the distribution of satellite educational television content while it can be used simultaneously for the survival of communication in case of emergency in rural zones, Using renewable energy sources and minimum consumption, no need to implement complex technological infrastructure, and thus obtaining the lowest environmental impact.


Many Koreans usually eat raw pond smelts, Hypomesus olidus, in the winter. This study was performed to evaluate the infection status with trematode metacercariae in pond smelts from January 1998 through February 1999. Among 1,305 fish collected, 459 were purchased from wholesale dealers in Chinchon-gun, Chungchongbuk-do, and the rest of them were caught with a casting net in Soyangho (Lake), Taehoman (Bay) and Paekkokchosuchi (Pond). Seven species of trematode metacercariae including two unidentified ones were detected from 1,305 pond smelts. The number of detected trematode metacercariae according to the species are as follow: Clonorchis sinensis 8, Holostephanus nipponicus 7, Cyathocotyle orientalis 24, Diplostomum sp. 14, and Metorchis orientalis 7. From the above results, it was confirmed that H. olidus plays a role as the second intermediate host of some kinds of trematode including C. sinensis in Korea. Our report shows possible clonorchiasis caused by eating raw pond smelts.


The initial boundary–value problem for the Korteweg–de Vries (KdV) equation on the negative quarter–plane, x < 0 and t > 0, is considered. The formulation of this problem is different to the usual initial boundary–value problem on the positive quarter–plane, for which x > 0 and t > 0. Two boundary conditions are required at x = 0 for the negative quarter–plane problem, in contrast to the one boundary condition needed at x = 0 for the positive quarter–plane problem. Solutions of the KdV equation on the infinite line, such as the soliton, cnoidal wave, mean height variation and undular bore solution, are used to find approximate solutions to the negative quarter–plane problem. Five qualitatively different types of solution are found, depending on the relation between the initial and boundary values. Excellent comparisons are obtained between these solutions and full numerical solutions of the KdV equation.


In this review, we provide an account of the recent progress in understanding electronic transport in disordered graphene systems. Starting from a theoretical description that emphasizes the role played by band structure properties and lattice symmetries, we describe the nature of disorder in these systems and its relation to transport properties. While the focus is primarily on theoretical and conceptual aspects, connections to experiments are also included. Issues such as short- versus long-range disorder, localization (strong and weak), the carrier density dependence of the conductivity, and conductance fluctuations are considered and some open problems are pointed out.


Abstract This article reviews acute and chronic lower extremity injuries in children, focusing mainly on those traumas typical of the pediatric population. The child is not just a small version of an adult, so physicians need a very detailed knowledge of the anatomy and physiologic changes occurring during growth to understand and evaluate the mechanism of trauma, and choose the most adequate management. In adolescents the most common lesion encountered affects the physes, which are still open. They predispose to injury as the weakest point in the kinetic chain, so those mechanisms responsible for ligamentous traumas in adults can cause physeal injuries in a skeletally immature patient. In association with them, apophyseal lesions are also very common, leading to avulsion injuries at the site of tendon origin or insertion, also called locus minoris resistentiae. Understanding these types of injuries is essential, specifically for the radiologist, because a missed diagnosis can lead to later complications such as growth arrest and osteoarthritis.


Both 17-estradiol and prolactin play important roles in the mammary gland, raising the possibility of functional cross-talk between the two signaling pathways. Here, we demonstrate that estrogen receptor- (ER) and - (ER) are both able to potentiate transcription from a Stat5-responsive promoter when activated by prolactin. Potentiation was observed not only in the presence of 17estradiol, but also in the presence of anti-estrogens such as tamoxifen and ICI 182,780. The magnitude of the response was dependent on cell-type: in the HC11 mouse mammary epithelial cell line ER potentiates transcription efficiently whereas ER showed low activity. Conversely, in COS-7 cells, both estrogen receptors were active. We show that activation domains in the N-terminus (AF-1) and the C-terminus (AF-2) of the ERs are dispensable for potentiation. The effects are dependent on the presence of an intact DNA-binding/hinge domain, which we show is capable of interacting with Stat5b in vitro and in HC11 cell extracts. We conclude that ER and ER act as coactivators for Stat5b through a mechanism which is independent of AF-1 and AF-2.


Phytophthora nicotianae is a devastating root and stem pathogen of tobacco (Nicotiana tabacum) in South Africa. Growers strive to control the resulting disease, known as black shank, with metalaxyl treatments and resistant cultivars. The aim of this study was to consider whether development of metalaxyl resistance in P. nicotianae has contributed to poor disease control and if recently developed cultivars with high levels of resistance require metalaxyl for effective control. One hundred and thirty-two isolates of P. nicotianae were screened for sensitivity to metalaxyl. P. nicotianae isolates from most tobacco farms were metalaxyl sensitive. Growth of most isolates was inhibited completely at 1.0 μg a.i./ml. However, isolates from the MKTV tobacco producing area showed EC50 values ranging from 1.02 μg a.i./ml to 3.57 μg a.i./ml. Twenty-one tobacco cultivars were planted and treated with and without metalaxyl in two different growing seasons to evaluate their resistance to P. nicotianae and the value of using metalaxyl. Hicks was the most susceptible cultivar. Vuma/3/46, LK30/40/60-1, and LK33/60 exhibited the greatest resistance to P. nicotianae. Use of metalaxyl in combination with moderately resistant cultivars such as NC60 × TL33 and LK10/80/60 effectively reduced black shank in the field. Resistant cultivars were healthy and no significant difference between metalaxyl treated and untreated plants was observed.


Spinal cord injury (SCI) is a catastrophic event with multiple comorbidities including spastic paralysis, sensory loss, autonomic dysfunction with sympathetic blunting, neurogenic orthostatic hypotension, neurogenic restrictive and obstructive lung disease, neuropathic pain, spasticity, neurogenic bladder, neurogenic bowel, immobilization hypercalcemia, osteopenia/osteoporosis, neurogenic obesity, and metabolic dysfunction. Cervical and thoracic SCI is all too often accompanied by traumatic brain injury (TBI), which carries its own set of comorbidities including headaches, seizures, paroxysmal sympathetic hyperactivity, aphasia, dysphagia, cognitive dysfunction, memory loss, agitation/anxiety, spasticity, bladder and bowel incontinence, and heterotopic ossification. This manuscript will review the etiology and epidemiology of dual diagnoses, assessment of both entities, and discuss some of the most common comorbidities and management strategies to optimize functional recovery.


The article examines the state policy in the field of physical education and sports of the USSR population in the early 1950s at the regional level – in the Penza region. It had the task to train physically strong, healthy, motivated «builders of communism», capable of high-performance labor and defence of the Motherland. The implementation of this area of activity of the Soviet leadership in the region involved the Committee on Physical Culture and Sport under the Penza Regional Executive Committee. The key areas of activity were the preparation of the TRP icons; creation of sports sections and colleges of judges; organization and holding of sports competitions, etc.


A structural model is constructed for the integral membrane protein, sensory rhodopsin I (SRI), the phototaxis receptor of the archaeon Halobacterium salinarium. The model is built on the template of the homologous bacteriorhodopsin (BR). The modeling procedure includes sequence alignment, a side chain rotamer search and simulated annealing by restricted molecular dynamics. The structure is in general agreement with previous results from mutagenesis experiments, chromophore substitution and room and cryogenic temperature spectroscopy. In particular, a residue near the beta-ionone ring of the retinylidene chromophore is found to be critical in maintaining the proper isomeric conformation of the chromophore; a layer of residues lying on the cytoplasmic side of the chromophore pocket is found to modulate the restraints around the C13 region of the chromophore, affecting the isomerizations around its 13 = 14 bond that are important to the protein's activity. The restraints in these regions are more stringent in SRI than in BR. The tightened restraints are chiefly due to van der Waals interactions, where the attractive and repulsive components play separable roles. Aromatic residues account for a majority of the restrictive interactions. It is hypothesized that the enhanced barriers due to these restrictions regulate the progress of SRI's photocycle, so that it can couple with the phototaxis reaction chain in the bacterium. A possibility is also suggested that conformational changes of the protein provide the signal recognized by the transducer.


A one-step, template-free method is described to synthesize porous carbons (PCs) in situ on a metal surface by using a room-temperature, atmospheric-pressure dielectric barrier discharge (DBD) plasma. This method not only features high efficiency, environmentally friendliness, and low cost and simple equipment, but also can conveniently realize large-area synthesis of PCs by only changing the design of the DBD reactor. The synthesized PCs have a regulated nestlike morphology, and thus, provide a high specific surface area and high pore volume, which result in excellent adsorption properties. Its applicability was demonstrated by using a PC-coated stainless-steel fiber as a solid-phase microextraction (SPME) fiber to preconcentrate polycyclic aromatic hydrocarbons (PAHs) prior to analysis by gas chromatography with flame ionization detection (GC-FID). The results showed that the fiber exhibited excellent enrichment factors (4.1×10(4) to 3.1×10(5)) toward all tested PAHs. Thus, the PC-based SPME-GC-FID provides low limits of detection (2 to 20 ng L(-1)), good precision (<7.8%), and good recoveries (80-115%) for ultra-sensitive determination of PAHs in real water samples. In addition, the PC-coated fiber could be stable enough for more than 500 replicate extraction cycles.


The need for timely and efficient treatment is assuming even greater significance, with pneumonia discharges increasing from 5,862 in 1992 to 7,870 in 1994. These two projects, involving a total of 13 hospitals, evaluated the timeliness of antibiotic administration for pneumonia patients. Baseline data revealed opportunities for improving process of care at all hospitals. After implementation of improvement plans, the majority of hospitals increased the percentage of patients receiving antibiotics within four hours of admission. This evaluation of the antibiotic delivery system can also be adapted to other diagnoses and medications.


Abstract Populations of Tribolium castaneum (Herbst) exposed to sublethal doses of irradiation (0.5–4.0 krad) each generation for as many as 25 generations had decreases in reproductive capacity and increases in sterility that were positively correlated with the size of the dose per generation, but not with the number of ancestral generations treated. Exposure of the selected populations to an acute dose of irradiation (2.0 krad) revealed no increase in tolerance to irradiation even after 25 generations of selection. Radioresistant populations would probably not arise from fertile survivors of irradiation disinfestation of bulk grain.


To improve the safety of recombinant vaccinia virus,a non-replicating vaccinia recombi- nant co-expressing rabies virus glycoprotein(RG) and nucleoprotein(RN) without a selectable marker was reconstructed. LacZ between fragment C and fragment K in non-replicating recombinant vaccinia virus VTKRG△CKlacZ was deleted and was substituted with rabies virus nucleoprotein by homologous recombination resulting in VTKRGΔCKRN. The recombinant vaccinia virus was screened by a two-step selection under, G418 and with White/Blue plaque color change as well as immunofluorescence. By Dot Blot analysis, RG gene and RN gene were shown to integrate stably into the non-replicating vaccinia recombinants even after 20 passages in CEF cells. The virulence of VTKRGΔCKRN was obviously less than that of VTKRG in naked mouse. The non-replicating characterization of VTKRGΔCKRN was also stable. It was proved that VTKRGΔCKRN could express RG and RN at the same time. VTKRGΔCKRN could elicit viral neutralizing antibody(VNA) similar to that of VTKRG by inoculated into the mice,and thus protect the animals from lethal challenge of rabies virus. It could elicit efficient viral neutralizing antibody(VNA) and protect the dogs from lethal challenge of rabies street strain SBD by intramuscular inoculation at dose of only 1.6×106PFU. This study confirmed the efficacy and safety of non-replicating recombinant vaccinia virus VTKRGΔCKRN.


Background: Breast cancer is the most common malignancy, and approximately 70% of breast cancers are estrogen receptor-α (ERα) positive. The anti-estrogen tamoxifen is a highly effective and commonly used treatment for patients with ER+ breast cancer. However, 30% of breast cancer patients fail adjuvant tamoxifen therapy and most of metastatic breast cancer patients develop tamoxifen resistance. Although increasing evidence suggests that microRNA (miRNA) dysregulation influences tamoxifen sensitivity, the mechanism of the cross-talk between miRNA and ERα signaling remains unclear. miR-575 has been reported to be involved in carcinogenesis and progression, however, the role of miR-575 in breast cancer remains limited. The aim of this study was to understand the mechanism of miR-575 in breast cancer tamoxifen resistance. Method: RT-qPCR was employed to assess miR-575 expression in breast cancer tissues and cell lines. The association of miR-575 expression with overall survival in patients with breast cancer was evaluated with KM plotter. Additionally, the effects of miR-575 on breast cancer proliferation and tamoxifen sensitivity were investigated both in vitro and in vivo. Bioinformatic analyses and luciferase reporter assays were performed to validate CDKN1B and BRCA1 as direct targets of miR-31-5p. The ERα binding sites in the miR-575 promoter region was validated with ChIP and luciferase assays. ERα interactions with CDKN1B, cyclin D1 or BRCA1 were determined by IP analysis, and protein expression levels and localization were analyzed by western blotting and immunofluorescence, respectively. Results: miR-575 levels were higher in ER+ breast cancer than in ER- breast cancer and patients with high miR-575 expression had a significantly poorer outcome than those with low miR-575 expression. ERα bound the miR-575 promoter to activate its transcription, and tamoxifen treatment downregulated miR-575 expression in ER+ breast cancer. Overexpression of miR-575 decreased tamoxifen sensitivity by targeting CDKN1B and BRCA1. CDKN1B and BRCA1 were both able to antagonize ERα activity by inhibiting ERα nuclear translocation and interaction with cyclin D1. Furthermore, miR-575 expression was found to be upregulated in ER+ breast cancer cell with acquired tamoxifen resistance, whereas depletion of miR-575 partially re-sensitized these cells to tamoxifen by regulation of CDKN1B. Conclusions: Our data reveal the ERα-miR-575-CDKN1B feedback loop in ER+ breast cancer, suggesting that miR-575 can be used as a prognostic biomarker in patients with ER+ breast cancer, as well as a predictor or a promising target for tamoxifen sensitivity.


Recent studies have suggested that sonic Hedgehog (Shh) signaling pathway is aberrantly activated in cancer stem cells (CSCs). A seven-herb Chinese medicinal formula composed of Amorphophallus rivieri Durieu, Oldenlandia diffusa (Wild) Roxb, Scutellaria barbata D. Don, Gynostemma pentaphyllum (Thunb.) Mak and Amomum cardamomum L, i.e. Qingyihuaji (QYHJ) formula, has been shown to inhibit proliferation of pancreatic CSCs by inhibiting Shh signaling pathway and thereby prolong the overall survival of pancreatic cancer patients. Mass spectrometry analysis revealed that baicalein is one of the major compounds of QYHJ formula. The objective of this study was to investigate the role of Shh pathway in pancreatic cancer and to examine the molecular mechanisms of baicalein involved in pancreatic cancer treatment. We examined the effects of baicalein on pancreatic CSCs both in vivo and in vitro. The results indicated that baicalein attenuated the pluripotency of pancreatic CSCs. Then, we investigated the underlying mechanism and found that nuclear transcription factors, such as Sox-2 and Oct-4 as well as members in Shh signaling pathway, e.g. SHH, SMO, and Gli-2, were downregulated after baicalein treatment. Furthermore, silencing Gli-2 expression by small interfering RNA decreased Sox-2 expression and blocked the inhibitory effects of baicalein, suggesting that the effects of baicalein may be mediated through inhibition of Shh pathway. Our results suggested that baicalein, an active compound in QYHJ formula, could suppress the self-renewal of pancreatic CSCs through inhibition of Shh signaling pathway.


We give a new construction of compact Riemannian 7-manifolds with holonomy $G_2$. Let $M$ be a torsion-free $G_2$-manifold (which can have holonomy a proper subgroup of $G_2$) such that $M$ admits an involution $\iota$ preserving the $G_2$-structure. Then $M/{\langle \iota \rangle}$ is a $G_2$-orbifold, with singular set $L$ an associative submanifold of $M$, where the singularities are locally of the form $\mathbb R^3 \times (\mathbb R^4 / \{\pm 1\})$. We resolve this orbifold by gluing in a family of Eguchi-Hanson spaces, parametrized by a nonvanishing closed and coclosed $1$-form $\lambda$ on $L$. Much of the analytic difficulty lies in constructing appropriate closed $G_2$-structures with sufficiently small torsion to be able to apply the general existence theorem of the first author. In particular, the construction involves solving a family of elliptic equations on the noncompact Eguchi-Hanson space, parametrized by the singular set $L$. We also present two generalizations of the main theorem, and we discuss several methods of producing examples from this construction.


This research deals with the Transnational Civil Procedure Principles adopted by the American Law Institute (ALI) and the International Institute for the Unification of Private Law (Unidroit), in Rome, in 2004. It emphasizes the importance of these Principles in the field of international commercial arbitration; these Principles are the first instrument as such that deals with civil procedure, especially because the experience of international conventions in this field was not satisfactory. This research stipulates the matters addressed by the Principles. It also clarifies the cases of their application, whether by the agreement of the parties or by the adoption of the principles by the legislature. In order to cope with the international development and to encourage the foreign trade, it was finally recommended that the legislature in the Arab countries should adopt these Principles as special civil procedure rules for the matters they address, namely the transnational adjudication. The legislature may also constitute a special court to apply the Principles to all disputes in the transnational commercial (and civil) matters.