This study investigates the complex ways in which personal life and social structure are interwoven in the construction of gender and identity in women managers and professionals. The 92 participants selected for the study are drawn from five different capital cities in Australia, from senior and middle positions in organizations, and from five different organizational contexts: private enterprise, public service, academia, trade unions, and community advocacy. Utilizing qualitative methodology, the research explores the respondents' organizational experiences and the interaction between the "public" and "private" domains in the structuring of their identity. Data was collected using an in-depth interview and an extensive written questionnaire.

The study integrates theoretical perspectives from a number of different disciplines so as to create a more adequate framework for understanding the complexities of women's organizational journeys. Drawing upon critical theory, identity theory, feminist theory, and the sociology of organizations, an effort is made to contribute both to theory development and to the understanding of the actual experiences of women in middle and senior positions in organizations. The three main structures that underpin the gender order are investigated in relation to the structuring of identity: the structure of power, the structure of cathexis, and the sexual division of labour.

In particular, the study considers how identity is implemented in the workplace, how workplace practices and experiences lead to a reconstruction of identity, the kinds of experiences which threaten that identity, and strategies that are used in coping with serious threats to identity. In addition, it examines some of the developmental influences on gender identity formation, the impact of current family structure in the maintenance of gender identity, the influence of the structure of cathexis in the workplace on gender identity, and the influence of workplace norms on gender identity.

Major conclusions drawn are that identity is constantly being constructed and reconstructed throughout adulthood; that women both implement some aspects of gendered identities at work, and resist other aspects of the organizational production of gender; that relationships and relating continue to be central to the construction of the identity of women managers and professionals; that a significant proportion of threats to identity in the workplace are related to gender; that there are a multiplicity of ways to be a "woman" manager or professional; that the structure of cathexis is resistant to change; that other gendered identities such as motherhood are undergoing considerable reconstruction; that the structure of cathexis in the workplace is problematic for women managers and professionals; that women professionals and managers both "fit in" and resist or challenge current organizational norms, expectations and practices; and that gender as a social category is continually reconstructed, reproduced and resisted in the interwoven workplaces of organizations and home.


Bispectral index (BIS) is used for monitoring anaesthetic depth with inhaled anaesthetic agents in the operating room but has not been evaluated as a monitor of sedation depth in the intensive care unit (ICU) setting with these agents. If BIS could predict sedation depth in ICU patients, patient disturbances could be reduced and oversedation avoided. Twenty ventilator-dependent ICU patients aged 27 to 80 years were randomised to sedation with isoflurane via the AnaConDa® or intravenous midazolam. BIS (A-2000 XP, version 3.12), electromyogram activity (EMG) and Signal Quality Index were measured continuously. Hourly clinical evaluation of sedation depth according to Bloomsbury Sedation Score (Bloomsbury) was performed. The median BIS value during a 10-minute interval prior to the clinical evaluation at the bedside was compared with Bloomsbury. Nurses performing the clinical sedation scoring were blinded to the BIS values. End-tidal isoflurane concentration was measured and compared with Bloomsbury. Correlation was poor between BIS and Bloomsbury in both groups (Spearman's rho 0.012 in the isoflurane group and -0.057 in the midazolam group). Strong correlation was found between BIS and EMG (Spearman's rho 0.74). Significant correlation was found between end-tidal isoflurane concentration and Bloomsbury (Spearman's rho 0.47). In conclusion, BIS XP does not reliably predict sedation depth as measured by clinical evaluation in non-paralysed ICU patients sedated with isoflurane or midazolam. EMG contributes significantly to BIS values in isoflurane or midazolam sedated, non-paralysed ICU patients. End-tidal isoflurane concentration appeared to be a better indicator of clinical sedation depth than BIS.


LYMPHOGRAPHY is the radiographic visualization of lymph vessels and nodes after intralympathic injection of a radiopaque substance. One application of lymphography is in the preoperative detection of lymphatic involvement by metastatic tumor. During the past 2½ years lymphography has been employed in the study of 109 patients with gynecologic cancer on the Obstetrics-Gynecology Service at the University of Miami School of Medicine. Twenty-seven patients were studied after undergoing radiotherapy for pelvic cancer. It soon became evident that irradiation of pelvic lymphatics could produce lymphographic findings that might be confused with metastasis to the lymphatic system. Examples of lymphographic alterations secondary to radiotherapy are presented in this report. Technique Lymphography is best performed when the patient is lying supine on a fluoroscopy table with the feet fixed in an extended position by adhesive tape. Lymphatic vessels are localized for cannulation on the dorsal aspects of the feet by injecting 1


The European Robotic Arm (ERA) is a contribution to the Russian Segment of the International Space Station Alpha. It will start operating on the Russian Segment during the assembly phase. ERA is designed and produced by a large industrial consortium spread over Europe with Fokker Space & Systems as prime contractor. In this paper, we will describe some of the overall design aspects and focus on the development of several mechanisms within ERA. The operation of ERA during the approach of its end effector towards the grapple interface and the grapple operation is discussed, with a focus on mechanisms. This includes the geometry of the end effector leading edge, which is carefully designed to provide the correct and complete tactile information to a torque-force sensor (TFS). The data from this TFS are used to steer the arm such that forces and moments are kept below 20 N and 20 N.m respectively during the grappling operation. Two hardware models of the end effector are built. The problems encountered are described as well as their solutions. The joints in the wrists and the elbow initially used a harmonic drive lubricated by MoS2. During development testing, this combination showed an insufficient lifetime in air to survive the acceptance test program. The switch-over to a system comprising planetary gearboxes with grease lubrication is described. From these development efforts, conclusions are drawn and recommendations are given for the design of complex space mechanisms.


The effects of Pratylenchus vulnus on rootstocks of eight commonly used Prunus spp. and one Pyrus communis were evaluated under greenhouse conditions during a 15-month period. In a first experiment, two almonds (Moncayo and Garrigues), one peach (GF-305), and two peach-almond hybrids (GF-677 and Adafuel) inoculated with 2,000 nematodes per plant proved to be good hosts of P. vulnus. Highest (P < 0.05) numbers of nematodes per gram of fresh root weight were recovered from Adafuel and GF-677. Root weights were higher in uninoculated compared to inoculated plants of all rootstocks, whereas top weights of uninoculated Garrigues, GF-305, and GF-677 differed (P < 0.05) from those of inoculated plants. In a second experiment, three plum (Marianna 2624, Myrobalan 605, and San Julian 655-2) and one pear (OHF-333) rootstocks were also found to be good hosts of P. vulnus, although significantly fewer nematodes were recovered from Myrohalan 605 roots than from the other three materials. Inoculated OHF-333 and San Julian 655-2 differed (P < 0.05) in root weights over uninoculated plants. Only inoculated San Julian 655-2 showed differences in top weights over uninoculated treatments. Rootstocks were poor or non-hosts for P. neglectus and P. thornei.


Hybrid nanostructures, composed of multi-component crystals of various shapes, sizes and compositions are much sought-after functional materials. Pairing the ability to tune each material separately and controllably combine two (or more) domains with defined spatial orientation results in new properties. In this review, we discuss the various synthetic mechanisms for the formation of hybrid nanostructures of various complexities containing at least one metal/semiconductor interface, with a focus on colloidal chemistry. Different synthetic approaches, alongside the underlying kinetic and thermodynamic principles are discussed, and future advancement prospects are evaluated. Furthermore, the proved unique properties are reviewed with emphasis on the connection between the synthetic method and the resulting physical, chemical and optical properties with applications in fields such as photocatalysis.


Using NADPH-d histochemistry, the effect of NMDA receptor antagonist MK-801 on the expression of nitric oxide synthase (NOS) in the dorsal horn of the spinal cord was investigated during inflammatory pain and hyperalgesia induced by injection of formalin into the right hind paw. The course of the change in the nitric oxide (NO) content of the lumbar intumescence was observed by measuring the ratio of nitrate/nitrite (NO3T/NO2T) and also the end product of NO. The results showed that the NOS expression and NO contents significantly increased 24 h after formalin injection, which were substantially inhibited when MK-801 was intrathecally injected 15 min prior to formalin injection or 12 h after formalin injection. The results suggest that the increases in the expression of NOS and NO contents in the dorsal horn of the spinal cord are mediated by activation of NMDA receptors during pain and hyperalgesia after formalin injection.


We use the following two well known bounds in our proofs. Lemma 1 (Chernoff-Hoeffding bound). Let X1, · · · , Xn be random variables with common support [0, 1] and E[Xi] = μ. Let Sn = X1 + · · ·+Xn. Then for all t ≥ 0, Pr[Sn ≥ nμ+ t] ≤ e−2t /n and Pr[Sn ≤ nμ− t] ≤ e−2t /n Lemma 2 (Bernstein inequality). Let X1, . . . , Xn be independent zero-mean random variables. If for all 1 ≤ i ≤ n, |Xi| ≤ k, then for all t > 0,


Patients with chronic lymphocyticleukemia (CLL) typically have innate/adaptive immune system dysregulation, thus the protective effect of coronavirus disease 2019 (COVID-19) vaccination remains uncertain. This prospective review evaluates vaccination response in these patients, including seropositivity rates by CLL treatment status, type of treatment received, and timing of vaccination. Antibody persistence, predictors of poor vaccine response, and severity of COVID-19 infection in vaccinated patients were also analyzed. Practical advice on the clinical management of patients with CLL is provided. Articles reporting COVID-19 vaccination in patients with CLL, published January 1, 2021–May 1, 2022, were included. Patients with CLL displayed the lowest vaccination responses among hematologic malignancies; however, seropositivity increased with each vaccination. One of the most commonly reported independent risk factors for poor vaccine response was active CLL treatment; others included hypogammaglobulinemia and age >65–70 years. Patients who were treatment-naive, off therapy, in remission, or who had a prior COVID-19 infection displayed the greatest responses. Further data are needed on breakthrough infection rates and a heterologous booster approach in patients with hematologic malignancies. Although vaccine response was poor for patients on active therapy regardless of treatment type, CLL management in the context of COVID-19 should aim to avoid delays in antileukemic treatment, especially with the advent of numerous strategies to mitigate risk of severe COVID-19 such as pre-exposure prophylaxis, and highly effective antivirals and monoclonal antibody therapy upon confirmed infection. Patients with CLL should remain vigilant in retaining standard prevention measures such as masks, social distancing, and hand hygiene.


Navigating the crossroads of sustainable infrastructure and innovative waste management, this research unveils the potential of waste honeycombs (WHCs)—an overlooked byproduct of apiculture—as a potent modifier for asphalt binder formulations. This endeavor addresses the dual challenge of enhancing road pavement sustainability and mitigating environmental degradation. A meticulous methodology evaluated the impact of varying WHC concentrations (5, 10, and 15 wt.%) on the asphalt binder, examining its attributes pre- and post-aging. Employing an array of analytical tools—thin-layer chromatography-flame ionization detection (TLC-FID); Fourier transform-infrared spectroscopy (FT-IR); scanning electron microscopy (SEM); thermogravimetric analysis (TGA); and a suite of conventional tests such as penetration, softening point, viscosity, ductility, dynamic shear rheometer (DSR), and multiple stress-creep recovery (MSCR)—provided a comprehensive insight into the binder's behavior. TLC-FID analyses revealed that WHC, with its 92 wt.% resin content, altered the SARA profile across distinct aging conditions, notably reducing asphaltene content, a factor linked to binder stiffness. The colloidal instability index (IC) further attested to this, pointing to a more thermodynamically stable system with WHC's inclusion. Meanwhile, FT-IR confirmed a physical interaction between WHC and asphalt without introducing new chemical entities. SEM observations highlighted the superior miscibility of WHC with asphalt, evidenced by a unique microtexture. With marked precision, TGA assessments unveiled a bolstering of asphalt's inherent thermal resilience consequent to a minor WHC integration. From the conventional tests, shifts in penetration, softening point, and viscosity were observed, with reduced viscosity, indicating improved workability. Lastly, while rutting potential was sensitive to WHC concentrations, fatigue resistance notably heightened with minor to moderate WHC inclusions. In essence, this pioneering study advocates for WHC's integration into asphalt formulations, offering enhanced road performance coupled with sustainable waste utilization. The findings underscore the synergy between environmental stewardship and infrastructural advancement.


Aim/Purpose: Fostering student engagement is one of the great challenges of teaching, especially in online learning environments. An educators' assumptions and beliefs about what student engagement is and how it manifests will shape the strategies they design to engage students in learning. However, there is no agreement on the definition of concept of student engagement and it re-mains a vague construct.

Background: Adopting the principles of user-centered design, the author maintains that to design learning experiences which better support student engagement it is important to gain insights into how students perceive and operationalize the concept of engagement in learning. The recent challenges of teaching effectively online prompted the author to reflect more deeply on the concept of engagement and how it might be achieved.

Methodology: In the tradition of reflective teaching, the author undertook an informal, qualitative inquiry in her classroom, administering a brief questionnaire to students in her online class. When the themes which emerged were integrated with other literature and findings from the author's earlier classroom inquiry, some insights were gained into how students 'operationalize' the concept of engagement, and weight was added to the authors' premise of the value of humanistic approaches to university teaching, the need for greater emphasis on student-teacher connection and the necessity of considering the affective domain alongside the cognitive domain in learning in higher education. The insights were brought together and visualized in a conceptual model of student engagement.

Contribution: The conceptual model presented in the present paper reflects the author's present 'mental model' of student engagement in classes online and, when the opportunity arrives, in face-to-face classes as well. This mental model shapes the authors' course design, learning activities and the delivery of the course. Although the elements of the model are not 'new', the model synthesizes several related concepts necessary to a humanist approach to under-standing student engagement. It is hoped that the model and discussion presented will be stimulus for further rich discussion around the nature of student engagement.

Findings: Interestingly, the affective rather than the cognitive domain framed students' perspectives on what engagement 'looks like to them' and on what teachers should do to engage them.

Recommendations for Practitioners: By sharing the process through which the author arrived at this understanding of student engagement, the author has also sought to highlight three key points: the importance of including the 'student perspectives and expectations' against which educators can examine their own assumptions as part of the process reflective teaching practices; the usefulness of integrating theoretical and philosophical frameworks in our understandings of student engagement and how it might be nurtured, and finally the necessity of affording greater influence to humanism and the affective domain in higher education. The findings emphasize the necessity of considering the affective dimension of engagement as an essential condition for cognitive engagement and as inextricable from the cognitive dimension of engagement.

Recommendations for Researchers: The emphasis in research engagement learning and teaching is on how we (the educators) can do this better, how we can better engage students. While the student perspective is often formulated from data obtained through surveys and focus groups, researchers in learning engagement are working with their own understandings (albeit supported by empirical research). It is crucial for deeper insight to also understand the students' conceptualization of the phenomena being researched. Bringing the principles of design thinking to bear on educational research will likely provide greater depth of insight.

Impact on Society: Empirical, formal, and structured research is undeniably essential to advancing human endeavor in any field, including learning and teaching. It is however important to recognize informal research in the form of classroom inquiry as part of teachers' reflexive practice is also legitimate and useful to advancing understanding of complex phenomenon such as student engagement in learning through multiple perspectives and experiences.

Future Research: Further research on the nature of student engagement in different contexts and against different theoretical frameworks is warranted as is empirical investigation of the premise of the value of humanism and the affective do-main in defining and measuring student engagement in higher education.


Aspergillus sinusitis are not uncommon. A multiplicity of etiologic factors are involved since any foreign body introduced in the sinus can be the starting point to an aspergillus cloud. The endodontic origin is difficult to establish. The authors will review this topic through a case report.


In this paper, we propose a novel framework for hand localization and pose estimation from a single depth image. For hand localization, unlike most existing methods that using heuristic strategies, e.g. color segmentation, we propose Hierarchical Hand location Networks (HHLN) to estimate the hand location from coarse to fine in depth images, which is robust to the complex environment and efficient. It first applied at a low-resolution octree of the whole depth image and produced coarse hand region and then constructs the hand region into a high-resolution octree for fine location estimation. For pose estimation, we propose Wide Receptive-filed (WR-OCNN) which is able to capture meaningful hand structure in different scales and estimate the 3D hand pose accurately. Experiments on two widely-used hand datasets(NYU dataset and ICVL dataset) demonstrate the effectiveness and superiority of the proposed framework.


Resistance to imatinib is a significant clinical issue, and the underlying mechanism of this resistance is multifactorial. The efficacy of imatinib in chronic myeloid leukemia (CML) in achieving a high remission rate and improving prognosis has seriously been challenged by the development of mutants of BCR-ABL gene, which resist the action of imatinib, which is a tyrosine kinase inhibitor. We present here a case of a 35-year-old male, a known case of CML on imatinib therapy, the patient eventually landed in blast crisis and succumbed to the disease and secondary infections.


The activist conjunction of sexual orientation and gender identity is questioned by demonstrating how the concerns of the transgender movement run contrary to an agenda of liberation from gender ideology. The confused vocabulary of trans discourse articulated in the language of somatic incongruence (so-called gender dysphoria) is exposed, using an analysis of the concept of somatic incongruence and the various interventions through which bodies are apparently restored to ideological congruence constructed upon, inter alia, gender, race, and age. The paper rejects transgender medical treatment and surgery as nothing but the most brutal affirmation of gender stereotypes and, in conclusion, calls for a radical and total disaffirming of gender, analogous to the termination of racial classification and segregation.


The types of detectors and the physics involved in present experiments are reaching a level of cost and complexity so great that it is preferable to implement a programmable trigger solution at al levels rather than a system realized with cabled logic. Experience demonstrates that the fine tuning on the trigger is often only achieved after running an experiment and analyzing the first data acquired. Recent advances in technology made real-time programmable algorithms down to the Level 1 trigger feasible. In this report a number of algorithms for the first level trigger have been simulated using one of the most advanced chips available. A fully-pipelined and programmable Level 1 trigger system sustaining a clock rate of 16 ns has been designed based on a modified version of the Data Wave chip.


Abstract : The report describes an approach whereby a commercial airport may select a snow removal system which is most suitable to its needs, taking account of the airport layout, local incidence of snow, and volumes and nature of air traffic handled. In all, over thirty systems are provided. Also contained in the report is an analysis of techniques for control of ice, slush and standing water on runways. Particular attention is given to methods of ice prevention using chemicals and sweepers. The analysis is carried out using the following techniques: flow diagrams to evaluate systems and calculate cost/effectiveness parameters, a traffic simulation model to measure delay costs due to runway closure, and a planning model to calculate total annual system costs consisting of: equipment operating costs and depreciation charges, labour cost, and delay costs to aircraft and passengers. The conclusions are classified with reference to the following areas: conclusions regarding implementation, conclusions for airport management, and conclusions for equipment manufacturers. (Author)


Router virtualization enables multiple virtual routers to be hosted on a physical shared substrate, and hence facilitates network management and experimentation. One critical issue of router virtualization is resource allocation of virtual routers. We explore this issue in the user-space design in order to allow extensibility. We develop a user-space load-aware virtual router monitor (LVRM) atop a commodity multicore architecture, with a key feature that it can dynamically manage CPU core resources among virtual routers based on their traffic loads. Also, LVRM adopts an extensible design so that each component can support different variants of implementation. We implement a proof-of-concept prototype for LVRM and empirically evaluate its performance overhead. Our work provides insights into resource management in user space in the context of router virtualization.


Characteristics of the "School Zones", their spatial location, arrangement, category of roads in the surroundings, user characteristics, etc., require a more serious approach and a more detailed analysis of specific problems, in order to prevent the occurrence of negative consequences of traffic. Amendments to the "Road Traffic Safety Act" of 2009, for the first time in domestic regulations, defined the term "School Zone", which created the legal basis and precondition for a more serious analysis of problems in the defined zones. Despite these significant shifts in regulation, problems of continuous operation are still pervasive. Determining the actual cause of traffic accidents in the "School Zones" and implementing adequate measures is lacking and most often comes down to the implementation of a universal set of measures without a more detailed analysis of specific locations. This paper analyzes traffic accidents that occurred in elementary "School Zones" in the city of Belgrade in 2018, with the aim of determining the potential dependence of street network characteristics and traffic accidents. The analysis was conducted for previously defined network attributes in the school environment: number of streets, traffic category, traffic groups and network type, on the basis of which the mentioned dependence was examined. The research results are presented and discussed in the paper.


Abstract. Ground-level ozone (O 3 ) pollution has been steadily
getting worse in most parts of eastern China during the past 5 years. The
non-linearity of O 3 formation with its precursors like nitrogen oxides
(NO x= NO + NO 2 ) and volatile organic compounds (VOCs) are
complicating effective O 3 abatement plans. The diagnosis from
space-based observations, i.e. the ratio of formaldehyde (HCHO) columns to
tropospheric NO 2 columns (HCHO  /  NO 2 ), has previously been proved to
be highly consistent with our current understanding of surface O 3
chemistry. HCHO  /  NO 2 ratio thresholds distinguishing O 3 formation
sensitivity depend on regions and O 3 chemistry interactions with
aerosol. To shed more light on the current O 3 formation sensitivity
over China, we have derived HCHO  /  NO 2 ratio thresholds by directly
connecting satellite-based HCHO  /  NO 2 observations and ground-based
O 3 measurements over the major Chinese cities in this study. We find
that a VOC-limited regime occurs for HCHO  /  NO 2  2.3, and
a NO x -limited regime occurs for HCHO  /  NO 2 >  4.2. The
HCHO  /  NO 2 between 2.3 and 4.2 reflects the transition between the two
regimes. Our method shows that the O 3 formation sensitivity tends to be
VOC-limited over urban areas and NO x -limited over rural and remote
areas in China. We find that there is a shift in some cities from the
VOC-limited regime to the transitional regime that is associated with a rapid drop
in anthropogenic NO x emissions, owing to the widely applied rigorous
emission control strategies between 2016 and 2019. This detected spatial
expansion of the transitional regime is supported by rising surface O 3
concentrations. The enhanced O 3 concentrations in urban areas during
the COVID-19 lockdown in China indicate that a protocol with simultaneous
anthropogenic NO x emissions and VOC emissions controls is essential for
O 3 abatement plans.


A novel example of AgSCF3-mediated oxidative radical trifluoromethylthiolation of α,α-diaryl allylic alcohols is presented, producing various α-aryl-β-trifluoromethylthiolated carbonyl ketones via radical neophyl rearrangement under mild conditions. This protocol involves formation of C(Ar)–C(sp3) and C(sp3)–S bonds in one step and tolerates a wide range of symmetrical and nonsymmetrical α,α-diaryl allylic alcohols.


Musculoskeletal disorders (MSD) comprise one of the most important occupational health issues in forestry professions. The purpose of the study was to examine the association among musculoskeletal disorders, antrhopometric and personal data, mental workload and occupational fatigue in forest professionals in northern Iran by means of the Nordic Musculoskeletal Questionnaire (NMQ), the National Aeronautics and Space Administration Task Load Index (NASA-TLX), and the Swedish Occupational Fatigue Inventory (SOFI). More than eight out of every ten subjects reported at least one MSD symptom during the past 12 months, with lower back (72.5%), feet and ankles (49%) and neck (41.2%) being the more frequently affected body regions. Similar MSD prevalences were reported for the period of seven days prior to data collection. Both the mental workload (grand mean 73.18±7.54) and occupational fatigue (grand mean 106.20±24.53) achieved high scores. MSD prevalence was found to be correlated with the SOFI score and the NASA-TLX score during the last year and seven days prior to data collection, respectively.Overall, the study results confirm the very demanding nature of the forest professions, which are characterized by high MSD prevalence, increased occupational fatigue and high mental workload. Given the small-scale forestry characteristics in the study area, taking measures such as introducing vocational training and promoting the use of personal protective equipment are some first necessary steps for the local forestry workforce.


Illusory correlation research has identified two factors that lead subjects to overestimate the relationship between particular categories of people and particular types of behavior: associative connections and shared infrequency. Three studies examined the nature of illusory correlation effects when both of these factors operated simultaneously. The results were consistent with previous shared infrequency effects only when infrequency and associations acted in concert. When undesirable behaviors were both infrequent and also associatively linked to a stimulus person's demographic group, there was an illusory correlation between membership in an infrequently appearing group and performance of infrequent, undesirable behaviors. More specifically, stimulus persons who were black, old, or of the opposite sex from the subject were rated more negatively when their demographic group appeared infrequently. Different illusory correlations were obtained when infrequency and associative links acted in opposition, undesirable behaviors being infrequent and desirable behaviors being associatively linked. Under these conditions, associative links overrode infrequency, and there was an illusory correlation between membership in an infrequently appearing group and performance of associatively linked, albeit frequent, desirable behaviors. More specifically, stimulus persons who were white, young, or of the same sex as the subject were rated more positively when their demographic group appeared infrequently.


Seeding nanoparticles in molten salts has been shown recently as a promising way to improve their thermo-physical properties. The prospect of such technology is of interest to both academic and industrial sectors in order to enhance the specific heat capacity of molten salt. The latter is used in concentrated solar power plants as both heat transfer fluid and sensible storage. This work explores the feasibility of producing and dispersing nanoparticles with a novel one pot synthesis method. Using such a method, CuO nanoparticles were produced in situ via the decomposition of copper sulphate pentahydrate in a KNO3-NaNO3 binary salt. Analyses of the results suggested preferential disposition of atoms around produced nanoparticles in the molten salt. Thermal characterization of the produced nano-salt suspension indicated the dependence of the specific heat enhancement on particle morphology and distribution within the salts.


S5, a hepatitis C virus protease inhibitor, displays partially saturable efflux in the Caco-2 system. In addition, the efflux can be reversed by cyclosporine, indicating that S5 may be a human P-glycoprotein (P-gp) substrate. S5 can also activate the ATPase activity in vesicle membranes containing mouse P-gp 1a and 1b, suggesting that S5 may be a substrate for mouse P-gp. The pharmacokinetics and tissue distribution of S5 were evaluated after intravenous and oral administration to wild-type and 1a/1b knockout mice. Plasma and kidney levels of this compound in knockout mice were transiently higher than those in wild-type mice only after oral dosing, indicating effective P-gp efflux occurs in wild-type mice. The levels of S5 in brain samples from knockout mice were higher than those from wild-type mice after both intravenous and oral administration, but much more significantly after intravenous administration. The levels in liver were four time higher in knockout mice than in wild-type mice after oral administration, but were not different between knockout and wild-type mice after intravenous administration. These results suggest that P-gp efflux limits exposure to S5 in the brain and liver, and that the effect is dependent on the route of administration.


Aims: A campaign to prevent initiation into drug injecting among street youth who have never injected drugs (NIDUs) was carried out in Montréal, Canada in 2005. Evaluation objectives were (1) to assess the campaign's ability to reach NIDU street youth and (2) to understand the campaign's effects on this population. Methods: A survey was conducted, as well as semi-structured interviews. Findings: The campaign enjoyed a high degree of visibility. It spoke to young NIDUs, causing them to reflect on both drug injecting and their own non-injection drug use. The campaign had a positive impact in terms of their views on drug injecting. Despite its limited scope, young NIDUs also considered the campaign to be a tool with the potential to contribute to preventing initiation into drug injecting among their peers. Conclusions: Media prevention campaigns are able to reach hidden populations through the use of bold and innovative techniques. Such campaigns can also contribute to influencing the attitudes and perceptions of these populations. However, more comprehensive injection prevention programs need to be established.


Allergic skin disease is a very common cause of itching in horses. The itching can severely affect the horse?s quality of life, leading to the horse wounding itself by biting or scratching, and it can reduce the utility of the horse. This 4-page fact sheet written by Rosanna Marsella, Nicky Craig, Carissa Wickens, and Samantha Brooks and published by the UF/IFAS Department of Animal Sciences explains how to manage allergic skin disease, control itching, treat secondary infections, and prevent the insect bites in the first place.https://edis.ifas.ufl.edu/an359


: The article presents a proposal for how to form cadet competencies in the process of initial adaptation to a military academy. A simplified model of cadet initial adaptation aimed at basic leadership competencies to achieve personal development in terms of ethics and morality, building self-discipline and social relations was proposed. The need to strengthen the system of education for security and defense within military departmental universities was identified. A survey of experts' opinions and a qualitative analysis of cases of competence formation of military students in the process of initial adaptation in selected land forces academies, i.e. the Polish Academy of Land Forces named after General Kosciuszko (AWL), the United States Military Academy (USMA) of West Point, the Austrian Theresian military academy i.e. Theresia Military Academy of the Federal Ministry of Defense (TM), the Greek military academy i.e. Military School "Evelpidon" (S.S.E). Only the direction of educational activities to ensure high quality command for strengthening security and defense was indicated.


Emergency portosystemic shunting has once again become a significant option in the management of bleeding esophageal varices and portal hypertension. The decision to perform such a shunt and the choice of shunt procedure requires a rational assessment of the pathophysiology and hepatoportal hemodynamics of the patient's disease and the manner in which it is anticipated that the selected procedure may alter portal flow. Since shunt surgery may interfere with hepatic transplantation, the patient's suitability as a future transplant recipient must also be considered in choosing a shunt procedure. Furthermore, if a shunt is to be performed on an emergency basis to control acute bleeding, this procedure must be done before the patient's condition deteriorates sufficiently to represent a prohibitive surgical risk.


REPORT OF A CASE An 8-year-old girl developed malaise, a sore throat, an enlarged tender liver, and adenopathy. Laboratory tests demonstrated elevated liver enzyme levels, a positive streptococcal screen, and a negative viral hepatitis profile (hepatitis B surface antigen, anti-hepatitis B surface antigen, anti-hepatitis B core antigen, and hepatitis A virus antibody). Six months later the patient developed severe generalized weight loss, most apparent on the lower extremities, polydipsia, and polyuria. A family history was noncontributory. On physical examination she had a "muscular habitus" with absence of subcutaneous fat over her entire body (Fig 1). Superficial veins were prominent on the legs (Fig 2). Her face revealed moderate subcutaneous atrophy with a few telangiectasias. On palpation, lymph nodes and liver were both slightly enlarged. The findings of examination of the genitalia were normal. There was no hypertrichosis, hyperpigmentation, or acanthosis nigricans noted. Laboratory data revealed elevated triglyceride levels, hyperinsulinemia,


Abstract This paper aims to assess the connections between knowledge management practices and a firm's potential and realized absorptive capacities. We use hierarchical multiple regression to test our theoretical framework using survey data collected from 94 Russian firms. By critically reviewing the antecedents of particular absorptive capacity subsets at the managerial, intra-organizational and inter-organizational levels, our study reveals the key knowledge management practices—work organization, information technologies, learning mechanisms, training and development and strategic management of knowledge—that enhance a firm's ability to acquire and assimilate knowledge (potential absorptive capacity) and to transform and exploit knowledge (realized absorptive capacity).


The dynamics of one-electron oxidation of guanine (G) base mononucleotide and that in DNA have been investigated by pulse radiolysis. The radical cation (G+*) of deoxyguanosine (dG), produced by oxidation with SO(4)-*, rapidly deprotonates to form the neutral G radical (G(-H)*) with a rate constant of 1.8 x 10(7) s(-1) at pH 7.0, as judged from transient spectroscopy. With experiments using different double-stranded oligonucleotides containing G, GG, and GGG sequences, the absorbance increases at 625 nm, characteristic of formation of the G(-H)*, were found to consist of two phases. The rate constants of the faster ( approximately 1.3 x 10(7) s(-1)) and slower phases ( approximately 3.0 x 10(6) s(-1)) were similar for the different oligonucleotides. On the other hand, in the oligonucleotide containing G located at the 5'- and 3'-terminal positions, only the faster phase was seen. These results suggest that the lifetime of the radical cation of the G:C base pair (GC+*), depending on its location in the DNA chain, is longer than that of free dG. In addition, the absorption spectral intermediates showed that hole transport to a specific G site within a 12-13mer double-stranded oligonucleotide is complete within 50 ns; that is, the rate of hole transport over 20 A is >10(7) s(-1).


ABSTRACT Sperm motility and hence male fertility strictly depends on proper development of the sperm tail and its tight anchorage to the head. The main protein of sperm tail outer dense fibers, ODF1/HSPB10, belongs to the family of small heat shock proteins that function as molecular chaperones. However, the impact of ODF1 on sperm tail formation and motility and on male fecundity is unknown. We therefore generated mutant mice in which the Odf1 gene was disrupted. Heterozygous mutant male mice are fertile while sperm motility is reduced, but Odf1-deficient male mice are infertile due to the detachment of the sperm head. Although headless tails are somehow motile, transmission electron microscopy revealed disturbed organization of the mitochondrial sheath, as well as of the outer dense fibers. Our results thus suggest that ODF1, besides being involved in the correct arrangement of mitochondrial sheath and outer dense fibers, is essential for rigid junction of sperm head and tail. Loss of function of ODF1, therefore, might account for some of the cases of human infertility with decapitated sperm heads. In addition, since sperm motility is already affected in heterozygous mice, impairment of ODF1 might even account for some cases of reduced fertility in male patients.


Omni mobile robots are one of the mobile robots that interact with humans in many areas where it is needed to be collaborative and accurate. Committing robotics with artificial intelligence-based controllers became nowadays mandatory for more association of these robots with distinct environments. This paper proposes the distinction of the 3WD Omni Vision feedback model between Simscape and actual information to obtain a surmised model. Study applying some artificial control procedures on this model for path planning and speed control as the artificial neural system and PSO optimization techniques for PID error and contrast these outcomes and compare them with conventional PID and Fuzzy Control techniques.


Socioeconomic status (SES) is a metric used to compare a person's social standing based on their income, level of education, and occupation. Students from low SES backgrounds are those whose parents have low income and have limited access to the resources and opportunities they need to aid their success. Researchers have studied many issues and solutions for students with low SES, and there is a lot of research going on in many fields, especially in the social sciences. Computer science, however, has not yet as a field turned its considerable potential to addressing these inequalities. Utilizing Natural Language Processing (NLP) methods and technology, our work aims to address these disparities and ways to bridge the gap. We built a simple string matching algorithm including Latent Dirichlet Allocation (LDA) topic model and Open Information Extraction (open IE) to generate relational triples that are connected to the context of the students' challenges, and the strategies they follow to overcome them. We manually collected 16 narratives about the experiences of low SES students in higher education from a publicly accessible internet forum (Reddit) and tested our model on them. We demonstrate that our strategy is effective (from 37.50% to 80%) in gathering contextual data about low SES students, in particular, about their difficulties while in a higher educational institution and how they improve their situation. A detailed error analysis suggests that increase of data, improvement of the LDA model, and quality of triples can help get better results from our model. For the advantage of other researchers, we make our code available.


Our evolving knowledge of the cellular and molecular mechanisms underlying atherosclerosis has helped uncover the underlying causes behind thrombotic complications of this disease. Most fatal coronary thrombosis result from fibrous cap rupture or superficial erosion. Recent research has established a role for matrix metalloproteinases in the regulation of aspects of plaque structure related to propensity to disrupt and provoke thrombosis. Inflammatory pathways impinge on proteinase activity and aspects of oxidative stress that may favour plaque disruption. Novel molecular imaging strategies may permit visualization of proteinase activity in vivo, providing a new functional window on pathophysiology.


Book synopsis: This book studies the history, literature and culture of Portuguese-speaking countries through the lens of utopia. The role of utopia in Portuguese literature is the object of fresh analyses ranging from Camoes to Goncalo M. Tavares, and Antonio Vieira to Jose Saramago. The chapters on Angola and Mozambique show how national identity received a major boost through utopian literature – Pepetela is the anchor in the former case, while dance is used as a crucial metaphor to reveal the tension between the colonial and postcolonial gaze in the latter case. The visions of paradise in Tupi tradition and missionary doctrine inform the approach to Brazil, developed by the study of the utopian dimension of the revolts of Canudos and Contestado. Regional contrasts and the quest for Brazilian national identity underlie the chapter on the cinema of Glauber Rocha and Walter Salles. These political and cultural acts can be compared to the strange case of Sebastianism in Portugal, here studied across four centuries of adaptation and transformation. Anarchist, Communist and Catholic political projects are analysed in the context of the early twentieth century to complete this evaluation of the uses and effects of utopian visions in these countries.


Fms-Like tyrosine kinase 3 (FLT3) mutations are related to poor prognosis in acute myeloid leukemia (AML), with the exception of acute promyelocytic leukemia (APL), in which the prognostic significance of this mutation is not firmly established even though it is more frequent than other FAB subtypes. We investigated FLT3 internal tandem duplications (FLT3/ITD) and/or D835 point mutations in both initial and relapse marrow samples from 120 AML patients, excluding APL. FLT3/ITDs were found in 18 initial and 16 relapse samples (15.0 and 13.3%, respectively). D835 mutations were found in one initial sample and 4 relapse samples. Two cases acquired FLT3/ITD at relapse, 4 cases lost mutations at relapse, and one had a different allele of FLT3/ITD at relapse. Patients who had FLT3/ITDs at initial diagnosis showed shorter median duration from diagnosis to relapse and shorter overall survival compared with those without mutations (median duration to relapse: 8.3 and 11.0 months, respectively, P = 0.074; overall survival: 12.2 and 20.8 months, respectively, P = 0.058). These findings were more pronounced when the FLT3/ITDs were acquired at relapse or discrepant patterns were noted between diagnosis and relapse (median duration to relapse: P = 0.047 and 0.044, respectively; overall survival: P = 0.002 and 0.038, respectively). In conclusion, the present study showed that patients with AML had heterogeneous patterns of FLT3/ITD or D835 mutations, either acquisition or loss of the mutations at relapse. The overall survival and relapse-free survival times were significantly shorter in the mutation acquisition group than in those with mutation loss at relapse.


With the mining industry transitioning through a well-publicised downturn as a result of lower commodity prices and unstable macro-economic conditions around the world, mine owners have sharpened their focus on increasing operational productivity and minimising unnecessary capital expenditure. The management of tailings, already perceived by many as simply a cost to the mine, is one of the key areas targeted for savings. With constraints on water availability and costs associated with water, particularly in arid environments, thickened tailings disposal becomes an attractive scenario. A central thickened discharge (CTD) tailings storage facility (TSF) was designed and commissioned at a phosphate mining operation in the Kingdom of Saudi Arabia. The design stage included comprehensive rheological and geotechnical characterisation of the tailings. The facility design was optimised for cost savings to store a specific thickened tailings product with a predicted beach slope profile and minimal supernatant pond, which influenced the perimeter embankment type and sizing. However, subsequent operational issues with variations in thickener performance and tailings properties, combined with a disconnection from the design stage to the construction and commissioning of the TSF, led to an inconsistently segregating tailings product with a significantly increased volume of water sent to the facility and beach slopes that were flatter than designed. This paper discusses the lessons learned from this project and the potential challenges and risks when there are large unforeseen variations in thickener performance and limited operator experience, which can lead to significantly more water to manage and reduced storage capacity compared to that designed. The paper also proposes key areas to focus on to mitigate against and lessen the impact of significant variations in the thickening process and tailings product sent to the TSF.


Reactive oxygen species (ROS) and signaling events are involved in the pathogenesis of endothelial dysfunction and represent a major contribution to vascular regulation. Molecular signaling is highly dependent on ROS. But depending on the amount of ROS production it might have toxic or protective effects. Despite a large number of negative outcomes in large clinical trials (e.g., HOPE, HOPE-TOO), antioxidant molecules and agents are important players to influence the critical balance between production and elimination of reactive oxygen and nitrogen species. However, chronic systemic antioxidant therapy lacks clinical efficacy, probably by interfering with important physiological redox signaling pathways. Therefore, it may be a much more promising attempt to induce intrinsic antioxidant pathways in order to increase the antioxidants not systemically but at the place of oxidative stress and complications. Among others, heme oxygenase (HO) has been shown to be important for attenuating the overall production of ROS in a broad range of disease states through its ability to degrade heme and to produce carbon monoxide and biliverdin/bilirubin. With the present review we would like to highlight the important antioxidant role of the HO system and especially discuss the contribution of the biliverdin, bilirubin, and biliverdin reductase (BVR) to these beneficial effects. The BVR was reported to confer an antioxidant redox amplification cycle by which low, physiological bilirubin concentrations confer potent antioxidant protection via recycling of biliverdin from oxidized bilirubin by the BVR, linking this sink for oxidants to the NADPH pool. To date the existence and role of this antioxidant redox cycle is still under debate and we present and discuss the pros and cons as well as our own findings on this topic.


The QoS based route optimization is a key issue of the wireless network, which is a NPC-hard multi-objective discrete optimization problem. In this paper, an efficient multi-objective artificial bee colony optimization algorithm based on Pareto dominance called MOABC is proposed to tackle this problem. The algorithm was evaluated on a set of different scale test problems and compared with GA based multi-objective optimization algorithm for this problem. The experimental results reveal very encouraging results in terms of the quality of solution and the processing time required.


Achieving effective solution for lasing on Silicon is a critical and important step for the successful implementation of Photonic Integrated Circuits in our quest to develop the next generation of ultrahigh bandwidth communication devices. In this overview paper various options of hybrid, monolithic and rare earth doping are discussed with the aim to offer the latest state-of-the-art on this topic. Monolithic integration of particular composition of Gallium and its alloys having the direct bandgap property and lattice constant similarity with silicon has been shown as promising. This is then compared with a Rare Earth doped Gallium Nitride approach as another possibility for the 'lasing on silicon' solution.


Getasan Subdistrict was the highest vegetable producer in Semarang Subdistrict.The purpose of this research was to analyze the transition pattern from anorganic to organic agriculture and agriculture farm profitability.
Data analysis method used in this research is the analysis of profitability, and analysis of R/C Ratio. The data used in this study are primary and secondary data. Samples were taken by purposive sampling method. Respondents in this study were vegetable farmers in Sub Getasan many as 56 people. Interview method used to interview the key person of the environment academia, government, and society.
Interview results showed that the pattern of land ownership of farmers own 82% owned by the area between 1.000-14.000 m2. Cropping pattern applied Getasan farmers are cropping intercropping plant species in accordance with market demand so that there is no definite pattern of cropping. The results showed profit received by farmers every year is Rp37.0268 million and R / C Ratio of organic farming is 5.47.


The aim of the study was to assess the prevalence of the MetS among patients
with CVD using the revised National Cholesterol Education Program Adult Treatment
Plan III (rNCEP ATP III) and International Diabetes Federation (IDF) definitions. STUDY DESIGN: A prospective observational study was conducted in the outpatient Department of
Cardiology, Kovai Medical Center and Hospital, a multispecialty hospital in Coimbatore. It
was approved by the KMCH ethics committee for research at Kovai Medical Center and
Hospital, Coimbatore on 22-10-2011. STUDY SITE: The study was conducted in the outpatient Department of Cardiology, Kovai Medical
Center and Hospital, a multi-specialty hospital in Coimbatore. STUDY PERIOD:
The study was carried over a period from June 2011 to December 2011 in Kovai
Medical Center and Hospital, Coimbatore.
INCLUSION CRITERIA: Both male and female patients having CVD were included in the study.
EXCLUSION CRITERIA: Pregnant women and patients with abdominal ascites were excluded from the study. Conclusion: The Indian subcontinent is undergoing epidemiological evolution as non-communicable
ailments like Coronary Heart Disease (CHD) and Type 2 Diabetes Mellitus (T2DM) are rapidly
replacing infections as the primary cause of morbidity and mortality. India has developed into
the "Diabetes Capital" of the globe and by the year 2020, is expected to have the maximum
number of individuals suffering from cardiovascular disease (CVD) (Yusuf S, Ounpuu S., 2001).
Approximately 7.8% of the United States (U.S) population has Diabetes Mellitus (DM), and it is
expected that the number of patients with DM will increase to 48.3 million by 2050 in the U.S.
and to 300 million worldwide in the year 2025, representing a 122% rise compared with 1995.
Even though the traditional cardiovascular jeopardy factors (e.g., smoking and hypertension) are
becoming more efficiently managed, a permanent increase of the so-called "cardiometabolic
risk" is prominent. Early from this century, the nomenclature "Metabolic Syndrome (MetS)" has
become more accepted to recognize a cluster of disorders together with obesity, dyslipidemia,
hypertension, and insulin resistance. It is the most important risk factor for CVD and DM in both
genders. Global cardiovascular jeopardy is the likelihood of affliction of a coronary episode or
stroke deriving from risk factors including metabolic factors (total cholesterol, high-density
lipoprotein cholesterol (HDL-c), blood glucose), hemodynamic factors (blood pressure), and
lifestyle factors (exercise, smoking), all changeable ahead of those nonmodifiable ones such as
age and gender.
Ongoing investigation is required to determine how best to define the MetS. Although it
is clear that the presence of the syndrome is associated with increased cardiovascular risk, the
levels of associated risk have not been clearly defined. Different projected definitions would
appear to result in diverse predictions of risk and appears to vary according to which components of the proposed definitions are present. Imam et al., reported a prevalence of 79.7% from
Pakistan, Bruno et al., reported a prevalence of 75.6% from the USA and Foucan et al., reported
a 77% prevalence of the MetS in diabetic Indian immigrants in the USA.
This prospective study revealed the prevalence rate of the MetS in Outpatient Department
of Cardiology clinics among patients with CVD using the IDF criteria as 41.1% and with revised
National Cholesterol Education Program Adult Treatment Plan III (rNCEP ATP III) criteria as
44.4%. When studying prevalence among the genders, females were more prevalent to the
syndrome than males which give an inference that females with MetS are prone to CVD and
other co-morbidities. But there were no significant differences in the cardiometabolic variables,
laboratory variables, hemodynamic variables and physical variables among male and female.
The findings from our study showed that the prevalence of the MetS increases with age. The
prevalence of the MetS in our subjects is high in both genders and increases with age thus posing
a latent high cardiovascular risk. The imperative clinical effect of the MetS was CVD. Also the risk for T2DM is higher,
and thereby DM is a foremost risk factor for CVD. Overall, MetS was related with a twofold
increase in the risk of CVD and stroke, and a 1.5-fold increase in risk of all-cause mortality.
Accordingly, individuals with MetS are at higher risk for cardiovascular outcomes than for allcause
mortality, although these patients are at elevated risk for either outcome compared with
those without this syndrome.
The alarming increase in obesity especially its central component consequential in MetS,
seems to be behind the twin pandemic of CVD and T2DM currently sweeping the Indian
subcontinent. From our study it was revealed that sedentary life-style and increased popularity
and easy-availability of energy-dense food are the dynamic force for this increasing hazard. It was found that in people without the syndrome has atleast one component of MetS and may
therefore be at an increased risk of cardiometabolic syndrome. And therefore community based
programmes to promote healthy living are needed to embark upon this catastrophe. Physicians
along with pharmacist and other healthcare professionals have a very important role to play in
this endeavor. Therefore larger prospective studies in other parts of India are necessary to
recognize the prevalence of the MetS along with the risk factors associated in cross sectional
population and in specific groups of high-risk patients.


Epics, the richest products of our cultural memory, involve every aspect of the traces left by the Turkish nation in history. It is possible to find many data about social, cultural, economic and religious life in our epics. These data shed light on monitoring the change and development of our nation, which has an archaic tradition of thousands of years, in many different geographies in the historical process. In the Turkish state tradition, on the solid foundations on which the executive-public relations are based, especially the sensitivity to spiritual values and sanctus has great importance. It is possible to see this sensitivity in the most striking form in our epics. In our study, based on the Turkish epics of different periods and conditions, the approach of the central hero / statesman to the saints and religious values will be examined comparatively.


Healthcare services face increasing challenges to provide accessible care to an equally increasing diversity ofpatient populations. This is clearly reflected in the linguistic diversity ofpeople living in Switzerland and can be seen mostplainly in the country 's public hospitals. After a literature review on language barriers in clinical services and the potential impact that interpreters can have in clinical outcomes, we describe how interpreters can be introduced in a primary care setting and how the quality of communication with foreign-language-speaking patients as well as their satisfaction with communication can be improved. Changes in the quality of inter - preter-mediated communication, as rated by the patients themselves, can be monitored and have a beneficial impact on the quality of care. This is important at a time of growing cultural and linguistic diversity in Switzerland and other countries, which requires healthcare systems to implement highquality professional interpreter services that ensure effective communication withforeign-language-speakingpatients.


The entropy power of a band-limited random process is the power of white Gaussian noise having the same entropy rate. Shannon's convolution inequality for entropy power states that the entropy power of the sum of two independent random processes is at least the sum of their entropy powers. This paper presents an improved version of Stam's proof of this inequality, which is obtained by mathematical induction from the one-dimensional case.


Background & Aims Cardiac myosin light chain kinase (cMLCK) plays an obligatory role in maintaining the phosphorylation levels of regulatory myosin light chain (MLC2), which is thought to be crucial for regulation of cardiac function. To test this hypothesis, the role played by ventricular MLC2 (MLC2v) phosphorylation was investigated in the phenylephrine-induced increase in twitch tension using the naturally-occurring mouse strain, C57BL/6N, in which cMLCK is down regulated. Methods and Results By Western blot and nanoLC-MS/MS analysis, cMLCKs with molecular mass of 61-kDa (cMLCK-2) and/or 86-kDa were identified in mice heart. Among various mouse strains, C57BL/6N expressed cMLCK-2 alone and the closest relative strain C57BL/6J expressed both cMLCKs. The levels of MLC2v phosphorylation was significantly lower in C57BL/6N than in C57BL/6J. The papillary muscle twitch tension induced by electrical field stimulation was smaller in C57BL/6N than C57BL/6J. Phenylephrine had no effect on MLC2v phosphorylation in either strains but increased the twitch tension more potently in C57BL/6J than in C57BL/6N. Calyculin A increased papillary muscle MLC2v phosphorylation to a similar extent in both strains but increased the phenylephrine-induced inotropic response only in C57BL/6N. There was a significant positive correlation between the phenylephrine-induced inotropic response and the levels of MLC2v phosphorylation within ranges of 15–30%. Conclusions We identified a new isoform of cMLCK with a molecular mass of 61kDa(cMLCK-2) in mouse heart. In the C57BL/6N strain, only cMLCK-2 was expressed and the basal MLC2v phosphorylation levels and the phenylephrine-induced inotropic response were both smaller. We suggest that a lower phenylephrine-induced inotropic response may be caused by the lower basal MLC2v phosphorylation levels in this strain.


Abstract The fifth-generation Pennsylvania State University–NCAR Mesoscale Model (MM5)-based regional climate model (CMM5) capability in simulating the interannual variations of U.S. precipitation and surface air temperature during 1982–2002 is evaluated with a continuous baseline integration driven by the NCEP–Department of Energy (DOE) Second Atmospheric Model Intercomparison Project Reanalysis (R-2). It is demonstrated that the CMM5 has a pronounced downscaling skill for precipitation and temperature interannual variations. The EOF and correlation analyses illustrate that, for both quantities, the CMM5 captures the spatial pattern, temporal evolution, and circulation teleconnections much better than the R-2. In particular, the CMM5 more realistically simulates the precipitation pattern centered in the Northwest, where the representation of the orographic enhancement by the forced uplifting during winter (rainy season) is greatly improved over the R-2. The downscaling skill, however, is sensitive to the...


Abstract : This guidebook is designed to help acquisition organizations benefit from their suppliers' use of CMMI for Development, which is a collection of best practices that addresses product development and maintenance activities throughout the product lifecycle. This guidebook also helps acquisition organizations avoid problems that can result from unrealistic expectations. High capability and maturity level ratings alone do not guarantee program success. This guidebook helps clarify what those ratings can and cannot do for a development program. It describes how acquirers can - interpret suppliers claims of achieving a CMMI rating - request, understand, interpret, and use supplier appraisal results, and - apply methods that leverage a supplier's process improvement initiatives.


Urinary tract infections (UTIs) are among the most common causes of hospitalization in children, with a rising prevalence of extended-spectrum beta-lactamase-producing organisms (ESBL). The purpose of this study was to identify risk factors and treatment outcomes of children with ESBL-UTI. A retrospective case-control study of hospitalized children was performed from July 2014 till December 2017. Medical records from patients with a positive urine culture were reviewed and included in the study if they met criteria for UTI. Cases were defined as ESBL-UTI, while controls were defined as non-ESBL-UTI patients. This study confirmed that there are certain risk factors, such as previous UTI, recent antibiotic use, urinary tract abnormalities, recent hospital admission, and nonrenal comorbidities, that are associated with ESBL-UTI. Most of the patients with ESBL-UTI responded to discordant antibiotics. Other significant outcomes in patients with ESBL-UTI included a longer length of stay and longer intravenous antibiotic therapy.


What role does leadership play in facilitating international cooperation in a complex global world beset by a variety of enduring and emerging transnational challenges? Scholars and practitioners alike have pointed to the importance of leadership in surmounting the barriers associated with reaching international agreements and achieving cooperative solutions. This chapter examines the relationship between international cooperation and leadership by critically reviewing the important contributions that have been made concerning the conceptualization of leadership, the motives actors have for engaging in leadership behavior, the sources of leadership influence, as well as the various modes of leadership that aspirants of international influence can utilize. It also highlights recent research that has focused on the demand side of leadership, leadership recognition, the factors that influence how followers select leaders, and the impact leadership exerts on international cooperation and negotiation outcomes. The chapter closes by pointing to new research frontiers that scholars of international leadership would profit from better addressing in the future, such as the need to increase our knowledge concerning shared leadership and the role of leadership in the post-negotiation and implementation phases of multilateral cooperative endeavors.


We experimentally demonstrate a passively Q-switched erbium-doped fiber laser (EDFL) operation by using a saturable absorber (SA) based on tungsten disulfide (WS 2 ). By depositing WS 2 thin film layer at the end of optical fiber ferrule, we fabricated a SA device. The SA is incorporated into an Erbium-doped fiber laser (EDFL) cavity to generate a Q-switching pulses train operating at 1559.8 nm. As a result, stable passively Q-switched EDFL pulses with maximum output pulse energy of 123.2 nJ, repetition rate of 104.1 kHz, and pulse width of 9.61 us are achieved when the input pump power is 142.1 mW at the wavelength of 980 nm. Full Text: PDF References C. Gao, W. Zhao, Y. Wang, S. Zhu, G. Chen, and Y. Wang, "Passive Q-switched fiber laser with SESAM in ytterbium-doped double-clad fiber", in 27th International congress on High-Speed Photography and Photonics (International Society for Optics and Photonics, 2007). CrossRef M. Ahmed, N. Ali, Z. Salleh, A. Rahman, S. Harun, M. Manaf, et al., "Q-switched erbium doped fiber laser based on single and multiple walled carbon nanotubes embedded in polyethylene oxide film as saturable absorber", Optics & Laser Technology 65, 25 (2015). CrossRef M. A. Ismail, F. Ahmad, S. W. Harun, H. Arof and H. Ahmad, "A Q-switched erbium-doped fiber laser with a graphene saturable absorber", Laser Phys. Lett. 10, 025102 (2013). CrossRef G. Sobon, J. Sotor, J. Jagiello, R. Kozinski, K. Librant, M. Zdrojek, L. Lipinska, and K. M. Abramski, "Linearly polarized, Q-switched Er-doped fiber laser based on reduced graphene oxide saturable absorber", Appl. Phys. Lett. 101, 241106 (2012). CrossRef N. H. M. Apandi, F. Ahmad, S. N. F. Zuikafly, M. H. Ibrahim, S. W. Harun, "Bismuth (III) Telluride (Bi2Te3) topological insulator embed in PVA as passive Q-switcher at 2 micron region", Photon. Lett. of Poland 8, 101 (2016). CrossRef J. Boguslawski, G. Sobon, K. Tarnowski, R. Zybala, K. Mars, A. Mikula, K. M. Abramski and J. Sotor, "All-polarization-maintaining-fiber laser Q-switched by evanescent field interaction with Sb2Te3 saturable absorber", Optical Engineering 55, 081316 (2016). CrossRef Z. Luo, Y. Huang, M. Zhong, Y. Li, J. Wu, B. Xu, H. Xu, Z. Cai, J. Peng, and J. Weng, "1-, 1.5-, and 2-um fiber lasers Q-switched by a broadband few-layer MoS2 saturable absorber", J. Lightwave Technol. 32, 4679 (2014). CrossRef N. N. Razak, A. A. Latiff, Z. Zakaria and S. W. Harun, "Q-switched Erbium-doped Fiber Laser with a Black Phosphorus Saturable Absorber", Photon. Lett. of Poland 9, 72 (2017). CrossRef D. Mao, Y. Wang, C. Ma, L. Han, B. Jiang, X. Gan, S. Hua, W. Zhang, T. Mei, and J. Zhao, "WS2 mode-locked ultrafast fiber laser", Sci Rep 5, 7965 (2015). CrossRef K. Wu, X. Zhang, J. Wang, X. Li, and J. Chen, "WS2 as a saturable absorber for ultrafast photonic applications of mode-locked and Q-switched lasers", Optics Express 23, 11453 (2015). CrossRef K. Lau, A. Latif, M. A. Bakar, F. Muhammad, M. Omar, and M. Mahdi, "Mechanically deposited tungsten disulfide saturable absorber for low-threshold Q-switched erbium-doped fiber laser", Applied Physics B 123, 221 (2017). CrossRef H. Chen, Y. Chen, J. Yin, X. Zhang, T. Guo, and P. Yan, "High-damage-resistant tungsten disulfide saturable absorber mirror for passively Q-switched fiber laser", Optics Express 24, 16287 (2016). CrossRef J. Lin, K. Yan, Y. Zhou, L. Xu, C. Gu, and Q. Zhan, "Tungsten disulphide based all fiber Q-switching cylindrical-vector beam generation", Applied Physics Letters 107, 191108 (2015). CrossRef H. Chen, Y. Chen, J. Yin, X. Zhang, T. Guo, and P. Yan, "High-damage-resistant tungsten disulfide saturable absorber mirror for passively Q-switched fiber laser", Optics Express 24, 16287 (2016). CrossRef K. Mohamed, B. Hamida, S. Khan, L. Hussein, M. Ahmat, E. Ismail, N. Kadir, A. Latif, S. Harun, "Q-switched erbium-doped fibre laser based on molybdenum disulfide and tungsten disulfide as saturable absorbers," Ukrainian Journal of Physical Optics, 18 (2017). CrossRef


Probabilistic graphical models are powerful tools for compactly representing complex probability distributions, efficiently computing (approximate) marginal and conditional distributions, and conveniently learning parameters and hyperparameters in probabilistic models. As a result, they have been widely used in applications that require some sort of automated probabilistic reasoning, such as computer vision and natural language processing, as a formal approach to deal with uncertainty. This paper surveys the basic concepts and key results of representation, inference and learning in probabilistic graphical models, and demonstrates their uses in two important probabilistic models. It also reviews some recent advances in speeding up classic approximate inference algorithms, followed by a discussion of promising research directions.


Sea ice algae contribute up to 25% of the primary productivity of polar seas and seed large‐scale ice‐edge blooms. Fluctuations in temperature, salinity, and light associated with the freeze/thaw cycle can significantly impact the photophysiology of ice‐associated taxa. The effects of multiple co‐stressors (i.e., freezing temperature and high brine salinity or sudden high light exposure) on the photophysiology of ice algae were investigated in a series of ice tank experiments with the polar diatom Fragilariopsis cylindrus under different light intensities. When algal cells were frozen into the ice, the maximum quantum yield of photosystem II photochemistry (PSII; Fv/Fm) decreased possibly due to the damage of PSII reaction centers and/or high brine salinity stress suppressing the reduction capacity downstream of PSII. Expression of the rbcL gene was highly up‐regulated, suggesting that cells initiated strategies to enhance survival upon freezing in. Algae contained within the ice‐matrix displayed similar levels of Fv/Fm regardless of the light treatments. Upon melting out, cells were exposed to high light (800 μmol photons · m−2 · s−1), resulting in a rapid decline in Fv/Fm and significant up‐regulation of non‐photochemical quenching (NPQ). These results suggest that ice algae employed safety valves (i.e., NPQ) to maintain their photosynthetic capability during the sudden environmental changes. Our results infer that sea ice algae are highly adaptable when exposed to multiple co‐stressors and that their success can, in part, be explained by the ability to rapidly modify their photosynthetic competence – a key factor contributing to algal bloom formation in the polar seas.


Geological mapping has been used as the process of making observations of geology in the field. A GIS-based methodology has also been used to produce a Landslide Susceptibility Zonation map for a landslide-prone area. The study area is located at Kampung Sungai Mekong, Jeli, Kelantan. The aim of this study was to prepare a geological and Landslide Susceptibility Zonation map of study area and identify the important factors controlling the landslides. There are three phases of geological mapping process which is preliminary research/planning, data collection and reporting. It includes laboratory analysis for the thin section of the rock. The detailed general geology, geomorphology, and lithostratigraphy of study area are needed in order to produce geological map. The study area is located in igneous rock lithology composed of granite and andesite. Granite plutons exposed in Jeli namely Kemahang Granite (Trgrkg). The age of Kemahang Granite and andesite assigned by previous study is to be Triassic and Permo-Triassic. Besides that, to produce a Landslide Susceptibility Zonation map, a statistical knowledge-based system integrated with a Geographical Information System environment was applied to assess the study area. This thesis explains a system to assess automatically vulnerability due to landslide of a region by categorizing landslide hazard using spatial and temporal causative factors. The expert system has input, understanding, expert and output modules and uses digital spatial data of causative factors of landslide. The causative factors considered are slope, relative relief, rock, soil and land use. Input accepts thematic images of contributing factors for landslides, understanding module interprets to extract relevant information as required by expert module consisting of a knowledge base and inference strategy categorizing region into different susceptibilities of landslide. Finally the output model provides a Landslide Susceptibility Zonation map. The results of the system suggest that 66.4% of the study area can be categorized as having low hazard and 33.6% as moderate hazard.


ABSTRACT Foreign trade offices (FTOs) are an important, little-understood element in the export promotion portfolio of U.S. state export promotion organizations. The value of these organizations is in dispute. In recent years California closed its FTOs in response to budgetary pressures, claiming that these organizations exist primarily to enhance the political standing of politicians rather than to act as effective export development tools. During the same period Washington State opened several new FTOs. Clearly the value of these organizations is in dispute. Another consideration in the effectiveness of U.S. exporters is the subnational contour of the American economic system. State business climates vary considerably, thereby influencing exporter success as well as those programs (such as FTOs) intended to improve firm performance. We hypothesize and find that (a) state entrepreneurial climate is positively related to state exports and (b) FTO network entry activities amplify the impact of state entrepreneurial climate on state exports. Implications for firms and policy makers are explored.


CONTEXT
Endoscopic transpapillary biliary drainage is the procedure of choice for biliary decompression in patients with unresectable pancreatic cancer. When ERCP is unsuccessful, the usual alternative is percutaneous transhepatic biliary drainage. Recently, the use of EUS-guided biliary drainage has been reported, but it is not clear whether it is feasible for this technique to find more widespread use as an alternative to failed ERCP. We herein describe our experience with two cases of unresectable pancreatic cancer associated with obstructive jaundice treated by EUS-guided biliary drainage.

CASE REPORT
Two men presented with obstructive jaundice due to unresectable pancreatic cancer. ERCP was unsuccessful in both cases because of complete tumor obstruction at the distal common bile duct. Both patients rejected the standard option of percutaneous transhepatic biliary drainage and EUS-guided biliary drainage was performed. The obstructed biliary system was successfully decompressed by the creation of a choledochoduodenal fistula and the insertion of a transduodenal biliary stent.

CONCLUSION
EUS-guided biliary drainage has the potential of replacing percutaneous transhepatic biliary drainage in unresectable pancreatic cancer with obstructive jaundice when ERCP is unsuccessful.


Background: Little is known about the prevalence of and factors associated with suicide ideation and suicide attempts among college youth in India. Aims: The aims were to estimate the prevalence of suicidal behaviours among Indian college students and identify potential risk factors for suicide ideation and attempts. Method: The study surveyed 1,817 undergraduate college students aged 18–24 years in Ahmedabad, Gujarat, with a questionnaire that assessed suicidal behaviours as well as stressful situations and life events. Logistic regression analysis was used to assess risk factors. Results: The prevalence of lifetime suicide ideation and lifetime suicide attempts was 11.7% and 4.0%, respectively. Suicide ideation was predicted by female gender, odds ratio (OR) = 1.41, 95% CI 1.01, 1.97, economic stress, OR = 1.17, 95% CI 1.11, 1.24, stress due to life events involving religious violence in the community, OR = 1.43, 95% CI 1.15, 1.78, and life events involving caste conflicts or caste discrimination, OR = 1.28, 95% CI 1.13, 1.46. Female gender and caste-related life events were not significantly associated with suicide attempts but economic stress and stressful experience of religious conflict continued to be significantly associated with lifetime suicide attempt, OR = 1.19, 95% CI 1.08, 1.31, and OR = 1.58, 95% CI 1.14, 2.17, respectively. Conclusions: In this sample, college students from low socioeconomic classes who faced economic difficulties, and students who experienced distress as a result of caste discrimination or caste conflict, and communal unrest, were at a higher risk for suicidal behaviour.


AIMS
Diabetic kidney disease (DKD) is the leading cause of end-stage kidney disease. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) showed excellent renoprotective effects; however, the underlying mechanism remains not fully understood. Previous studies have revealed the importance of ferroptosis, which is closely related to oxidative stress, in the progression of DKD. In the current study, we hypothesized that SGLT2i could relieve ferroptosis and thereby alleviate renal injury in DKD due to their anti-oxidative stress effects.

RESULTS
Typical changes of ferroptosis including massive lipid peroxidation, compromised antioxidant capability, and iron overload were found in db/db mice and high glucose/high fat (HG/HF)-treated HK-2 cells. Furthermore, increased expression of hypoxia inducible factor 1α (HIF1α) and heme oxygenase 1 (HO1) was observed in db/db mice and HG/HF-treated HK-2 cells as well. Dapagliflozin treatment significantly ameliorated the ferroptosis-related changes via attenuating over-activation of the HIF1α/HO1 axis in vivo and in vitro. Besides, downregulation of the HIF1α/HO1 axis alleviated ferroptosis, while overexpression of HIF1α and HO1 aggravated ferroptosis induced by HG/HF in HK-2 cells.

INNOVATION AND CONCLUSION
This study revealed that SGLT2i played a renoprotective role in DKD, at least in part, through alleviating HIF1α/HO1 mediated ferroptosis.


Predictions of environmental models are affected by unavoidable and potentially large uncertainty. When models are applied to understand dominant controls of the system under study, uncertainties will reduce our ability to choose between competing hypotheses. When they are used to support decision-making, uncertainties will reduce our ability to discriminate between different management options and undermine the defensibility of the decision-making process. Global Sensitivity Analysis (GSA) provides quantitative information about the contribution to the uncertainty in the model output arising from different input factors like, for instance, model parameters, boundary conditions or forcing data. GSA thus provides insights into the model behavior and potential for simplification, indicates where further data collection and research is needed or would be beneficial, and enhances the credibility of the modelling results. In this paper, we present a novel method to GSA based on the comparison of the unconditional distribution of the model output, i.e. when all input factors vary, and the conditional distribution when one of the input factors is fixed. The main advantages of our strategy are that, in contrast to other GSA approaches, it works equally well regardless of the output distribution shape, e.g. skewed or not-skewed; it can be focused on specific regions of the output distribution, for instance extreme values; and it provides additional information about the input ranges that map into these output regions (so called Factor Mapping). We test the method using a real-world hydrological modelling application, and compare it to a well-established method of variance-based sensitivity indices (Sobol's method). We finally discuss its advantages and limitations and outline directions for further research.


Volcanic eruptions in Iceland generally start with an increase in tremor levels. These signals do not have clear onset, like many earthquakes. As the character of the tremor signal is variable from one volcano to another, locating the source of the tremor signal may require different techniques for different volcanoes. Continuous volcanic tremor varied considerably during the course of the Eyjafjallajökull summit eruption, April 14th to May 22nd 2010, and was clearly associated with changes in eruptive style. The tremor frequencies ranged between 0.5 and 10 Hz, with increased vigour during an effusive and explosive phase, in comparison with purely explosive phases. Higher-frequency tremor bursts early in the eruption were caused by processes at the eruption site. Location of the tremor using a method based on differential phase information extracted from inter-station correlograms showed the tremor to be stable near the eruption vent, through time, for signals between 0.5 Hz and 2 Hz. Analyses of power variations of the vertical component of the tremor with distance from the eruption site are consistent with tremor waveform content being dominated by surface waves in the 0.5-2 Hz frequency range. The tremor source depth was argued to be shallow, less than about 1 km. The attenuation quality factor (Q) was found to be on the order of Q = 10-20 for paths in the area around Eyjafjallajökull and Q = 20-50 for paths outside the volcano. The pattern of radiated wave energy from the tremor source varied with time, defining ten different epochs during the eruption. Thus the tremor-source radiation did not remain isotropic, which needs to be considered when locating tremor based on amplitude, i.e. azimuthally variable source radiation.


Leveraging domain knowledge including fingerprints and functional groups in molecular representation learning is crucial for chemical property prediction and drug discovery. When modeling the relation between graph structure and molecular properties implicitly, existing works can hardly capture structural or property changes and complex structure, with much smaller atom vocabulary and highly frequent atoms. In this paper, we propose the Contrastive Knowledge-aware GNN (CKGNN) for self-supervised molecular representation learning to fuse domain knowledge into molecular graph representation. We explicitly encode domain knowledge via knowledge-aware molecular encoder under the contrastive learning framework, ensuring that the generated molecular embeddings equipped with chemical domain knowledge to distinguish molecules with similar chemical formula but dissimilar functions. Extensive experiments on 8 public datasets demonstrate the effectiveness of our model with a 6\% absolute improvement on average against strong competitors. Ablation study and further investigation also verify the best of both worlds: incorporation of chemical domain knowledge into self-supervised learning.


This book about the Swedish Health Service expodes popular misconceptions about that enigmatic country. It is not a welfare paradise and its suicide rate, far from being the highest, is one of the lowest in Europe. Medical care is not free, patients paying Kr. 7 (about 70p) for each consultation, which includes investigations and referrals which follow from it. They pay the same fee whether they go to hospital outpatient department or to district officers (the G.P. equivalent), but many in the large towns go to private practirtioners despite having to pay a much larger fee, only part of which can be reclaimed later. The reform of the Health Service in 1970 seems to have been far less radical than our reorganization. It left the system tripartite, with hospitals getting the highest priorities because the influence of the teaching hospital specialists still determines health priorities. The primary care system remains isolated, with district officers working in solo practices. Tihe much vaunted delegation of clinical work to attached nurses in well equipped health centres, which seemed such a model to us nearly a decade ago, is still confined to pilot experiments, not a general rule. The same is true of group practice, which, though actively sponsored by the Swedish Medical Association, expands far more slowly than expected. One change brought about by the reforms of 1970 is in doctors' contracts, designed to foster equalization of incomes within the profession. Paymenit is now by salary for hours worked instead of by partial salary wi.th consultation fee, which stimulated competition, a change welcomed by junior doctors because it improved their working conditions and limited their daily working hours but disliked by senior doctors because it "deprfessionalized" medical practice and converted it to "conmon work." The author is an American, whose work is sponsored by an American foundation interested in models for health services. To what extent Sweden provides models for the evolution of our National Health Service is a rmater of individual opinion, but more effective regionalization of health services seems to this reviewer at least one example.


Building on Simmel's theoretical foundations, sociological process theorists continue to challenge mainstream social theory. So far, however, they have rarely relied on formal modeling. The author argues that recent advances in computational modeling offer tools to explore the emergence of social forms in the Simmelian tradition. Thanks to common foundations in both epistemology and ontology, these two fields can benefit from drawing more explicitly on each other. The process‐theoretic tradition in social theory and contemporary agent‐based models shift theorizing from nomothetic to generative explanations of social forms, and from variable‐based to configurative ontologies. In order to formalize sociational theory, the author focuses on how to model dynamic social networks and emergent actor configurations.


Salmonella is closely related with human health of modern society which has concern increased in livestock goods consumption as well as give economic damage throughout the chicken industry such as farm, hatchery, slaughter house and processing plant. From 2007 to 2011, this study investigated Salmonella prevalence from 200 old hen delivery trucks which deliver old egg-laying hens and broiler breeders in Korea. The prevalence of Salmonella species was 38.0% in old hen delivery truck. Serogroup C1 was the most frequently detected serogroup of Salmonella, followed by the serogroups D1, C2 and B. A total of 25 serotypes were identified and Salmonella infantis was the most frequently isolated serotype. In addition, we applied disinfectant to old hen delivery truck for the reduction of Salmonella contamination. The disinfectant consists of formaldehyde, glutaladehyde and quaternary ammonium compound was applied to the trucks. Salmonella isolation rate was significantly decreased after disinfection from 38.0% to 7.5%. Disinfectant could not effectively reduce Salmonella contamination at a dilution of 1:200 which is recommended by manufacturer, but Salmonella isolation rate was significantly decreased at a dilution of 1:50. Since old hen delivery truck could be a potential vector to carry Salmonella into farms and abattoirs, chicken delivery truck should be disinfected thoroughly and sufficiently to control contamination of farms and abattoirs.


The wide variety of aromatic plants and their use represent great economic value worldwide, due to the numerous therapeutic properties available. The Lavandula genus stands out in the world economy, mainly due to the production of essential oil, which can be extracted from its leaves or flowers, being widely used in the cosmetic, food and pharmaceutical industries. However, the therapeutic properties of this essential oil can be impaired due to its low aqueous solubility, high volatility and low physical-chemical stability. The association of essential oil with nanostructured systems can be a promising and efficient alternative to overcome these limitations, providing greater stability of the active compounds, protection against oxidation, photodegradation and thermal degradation processes, and thus, promoting a potential enhancement of efficiency. Thus, the objective of the study was to carry out a review of the literature about the available research that uses nanostructured systems to encapsulate the essential oil of different lavender species. The search was carried out in April 2020, in the electronic databases Web of Science, PubMed and ScienceDirect. The descriptors and keywords used were: nano *, lavender, Lavandula, followed by the Boolean operators AND; OR, and the year of publication of the articles was not defined. Eight articles were found that adequately met the inclusion criteria, which were published between the years 2017 to 2020. From the results found, it is believed that nanotechnology can be a promising alternative to protect the active compounds of lavender essential oil against factors that can impair their stability, as well as, guarantee or even increase their effectiveness, with the possibility of decreasing dose and consequently side effects.


Both Ca2+ and the actin cross-bridge reaction itself can activate contraction in myofilaments. We are interested in identifying ligands which modify one or both mechanisms of contractile activation with high affinity and specificity. Results presented here suggest that the benzimidazole-substituted pyridazinone, UD-CG 212 Cl, potently modulates myofilament activation by the cross-bridge reaction. Cross-bridge-mediated activation was studied by varying the population of force-generating (strong) cross-bridges with inorganic phosphate (Pi). Addition of Pi to detergent-extracted (skinned) canine ventricular preparations reduces the population of strong cross-bridges, which causes reduced myofilament force and Ca2+ sensitivity. Increased Pi concentration ([Pi]) also favors cross-bridge-mediated myofilament activation, so cooperativity increases. The decreased Ca2+ sensitivity produced by Pi was reversed by a racemic mixture of 10(-10) M UD-CG 212 Cl, but this agent had no effect on maximum force or cooperativity. In experiments with stereoisomers, only (+)-UD-CG 212 Cl stimulated force. At higher doses (10(-6)-10(-4) M), submaximal but not maximal force decreased and (-)-UD-CG 212 Cl was the active stereoisomer. Neither Pi nor UD-CG 212 Cl affected Ca2+ binding to myofilament troponin C (TnC). Thus, UD-CG 212 Cl appears to reverse Pi-induced decreases in submaximal force via high-affinity binding to a myofibrillar domain not directly involved with myofibrillar TnC-Ca2+ binding. The actions of UD-CG 212 Cl were further investigated by reducing [ATP] as another means of varying the cross-bridge population.(ABSTRACT TRUNCATED AT 250 WORDS)


Inactivation of the enzyme L-aspartase from Escherichia coli by the substrate analog aspartate beta-semialdehyde has previously been shown to occur by the mechanism-based conversion to the corresponding product aldehyde, followed by covalent modification of cysteine-273 (F. Giorgianni et al. (1995) Biochemistry 34, 3529). Inactivation by the product analog, fumaric acid aldehyde (FAA), has now been examined directly by adding a reduction step to the modification protocol in order to stabilize the resulting enzyme-FAA derivative(s). HPLC and mass spectrometric analyses of proteolytic digests of inactivated L-aspartase have confirmed the modification at cysteine-273, and have also identified an additional modified peptide. The inactivation at this additional site involves a crosslink between cysteine-140 and an adjacent lysine. Site-directed mutagenesis studies have shown that cysteine-140 is a very reactive and accessible nucleophile that is not, however, directly involved in enzyme activity. The adjacent lysine-139 that is modified does appear to play a role in substrate binding. A double mutant in which both of the reactive cysteines have been replaced is almost completely insensitive to modification by these substrate and product analogs.


Malignant gliomas are the most lethal form of primary brain tumors. Despite advances in cancer therapy, the prognosis of glioma patients has remained poor. Cytochrome c (Cytc), an endogenous heme‐based protein, holds tremendous potential to treat gliomas because of its innate capacity to trigger apoptosis. To this end, a hybrid cytochrome c‐chlorotoxin (Cytc‐CTX) protein was biosynthesized to enable cellular uptake of the cell impenetrable Cytc using CTX transporters. A nucleotide sequence containing 1 : 1 Cytc and CTX was constructed and separated by a hexahistidine‐tag and an enterokinase cleavage site. The sequence was cloned into a pBTR1 plasmid, expressed in Escherichia coli, purified via 2‐dimensional chromatography. The identity and size of the protein were determined by Western blot and mass spectrometry. Cytc in this soluble hybrid protein has similar structure and stability as human Cytc and the hybrid protein is endocytosed into a glioma cell line, while displaying potent cytotoxicity and a favorable therapeutic index. Its facile, low‐cost, and high yield synthesis, biocompatibility, and robustness suggest that the hybrid protein is a promising candidate for antiglioma drug evaluation.


This paper uses the financial statements of special purpose entities (SPEs) for explaining the origin and destination of dividend, interest, and royalty flows passing the Netherlands. We find that Bermuda is the most important destination for royalty flows. These flows come from Ireland, Singapore and the United States. For dividend and interest payments the geographical pattern is more widespread. We find a substantial tax reduction for royalties by using Dutch SPEs compared to a direct flow between the origin and destination country. However, we cannot find such tax savings for dividends and interest with an approximation based on statutory tax rates. This Discussion Paper reports research on the financial flows already presented in the CPB Policy Brief of 24 January 2019: Conduit country the Netherlands in the spotlight. (This abstract was borrowed from another version of this item.)