Anacardiaceae is a moderately large family. It includes 74 genera and approximately 600 species. The family has an extensive fossil record that dates back at least to the Maastrichtian (Upper Cretaceous), and that consists to a large extent of leaf impressions. In this work, the description of the leaf architecture of 61 genera of Anacardiaceae is presented. The leaves (or leafl ets) of 102 species were cleared, mounted and observed under both dissection and compound microscopes.


In this article, We focus on silicon nanowire (SiNW)-based resonators that were fabricated and employed to sense aerosol nanoparticles (NPs) by measuring resonant frequency shifts induced by the mass of stuck NPs. The fabrication of SiNW arrays was performed using inductively coupled plasma (ICP) cryogenic dry etching and multiple thermal oxidations. The SiNWs were coated with gold (Au) for contacting to the homebuilt electrostatic NP sampler to collect the flowing NPs. A piezoelectric shear actuator mounted in the frequency measurement system was used to excite the SiNW sensors into resonance. Tested in a titanium dioxide (TiO2) aerosol sampling with a total concentration of ~8,500 NPs/cm3, the sensor displayed its feasibility as a nanobalance to detect aerosol NPs in the femtogram scale with a mass sensitivity of 7.1 Hz/fg and a mass resolution of 31.6 fg. To extend the operating life of the sensor, an ultrasonic removal method was used to detach the adhered NPs.


Abstract Background: Bacillus Calmette-Guerin (BCG) is the most effective intravesical therapy for non-muscle invasive bladder cancer (NMIBC), but patients can fail or supply shortages can develop. For BCG failures, radical cystectomy is recommended. However, in patients who desire bladder preservation or are poor surgical candidates, alternative salvage intravesical therapies should be explored. Objective: To determine whether dual sequential intravesical gemcitabine and docetaxel is effective in treating NMIBC. Methods: We evaluated our initial experience with 45 patients treated with intravesical gemcitabine and docetaxel between June 2009 and May 2014. Patients were treated with 6 weekly instillations of gemcitabine (1 gram of gemcitabine in 50 ml of sterile water) followed immediately by docetaxel (37.5 mg of docetaxel in 50 mL of saline). Treatment success was defined as no bladder cancer recurrence and no cystectomy. Intention-to-treat analysis was performed using the Kaplan Meier method. Results: Forty-five patients received treatment with a median overall follow-up of 15 months. Median follow up for treatment success was 6 months in all patients and 13 months for responders. Five patients were unable to tolerate a full induction course. Treatment success was 66% at first surveillance, 54% at 1 year, and 34% at 2 years after initiating induction. Ten patients received cystectomy (median of 5.6 months from starting induction) with no positive margins or lymph nodes on final pathology. Conclusions: Sequential dual intravesical gemcitabine and docetaxel can salvage some patients in a challenging NMIBC cohort.


Assortative mating in phenotype in human marriages has been widely observed. Using genome-wide genotype data from the Framingham Heart study (FHS; number of married couples = 989) and Health Retirement Survey (HRS; number of married couples = 3,474), this study investigates genomic assortative mating in human marriages. Two types of genomic marital correlations are calculated. The first is a correlation specific to a single married couple "averaged" over all available autosomal single-nucleotide polymorphism (SNPs). In FHS, the average married-couple correlation is 0.0018 with p = 3×10−5; in HRS, it is 0.0017 with p = 7.13×10−13. The marital correlation among the positively assorting SNPs is 0.001 (p = .0043) in FHS and 0.015 (p = 1.66×10−24) in HRS. The sizes of these estimates in FHS and HRS are consistent with what are suggested by the distribution of the allelic combination. The study also estimated SNP-specific correlation "averaged" over all married couples. Suggestive evidence is reported. Future studies need to consider a more general form of genomic assortment, in which different allelic forms in homologous genes and non-homologous genes result in the same phenotype.


The site of Mwanganda's Village, located along a paleochannel in northern Malawi, is one of only a few sites that have characterized the Middle Stone Age (MSA) of Malawi for decades (Clark & Haynes, ; Clark et al., ; Kaufulu, ). The Malawi Earlier‐Middle Stone Age Project has re‐examined the site using new mapping and chronometric tools in order to reinterpret the site's significance within the context of current debates surrounding human origins and the potential role the environment played in shaping human behavior. The new data do not support the previous hypothesis that the site was an elephant butchery location (contra Clark & Haynes, ; Clark et al., ; Kaufulu, ). Instead, the evidence shows successive colonization of riparian corridors by MSA hunter‐gatherers focused on exploiting localized resources during periods of generally humid climates while other lakes desiccated across Africa. We challenge the hypothesis that stable and intermediately high lake levels within the African Rift Valley System (sensu Trauth et al., ) catalyzed the evolution of regional interaction networks between 42 and 22 ka. Instead, we interpret the evidence to suggest that regional variants of technology persist into the late MSA as foragers focused on exploiting resources from local catchments.


Over the last few years, there has been an increase in the number of multimedia-enabled devices (e.g. cameras, smartphones, etc.) and that has led to a vast quantity of multimedia content being shared on the Internet. For example, in 2010 thirteen million hours of video uploaded to YouTube (http://www.youtube.com). To usefully navigate this vast amount of information, users currently rely on search engines, social networks and dedicated multimedia websites (such as YouTube) to find relevant content. Efficient search of large collections of multimedia requires metadata that is human-meaningful, but currently multimedia sites generally utilize metadata derived from user-entered tags and descriptions. These are often vague, ambiguous or left blank, which makes search for video content unreliable or misleading. Furthermore, a large majority of videos contain people, and consequently, human movement, which is often not described in the user entered metadata.


Three studies test whether people engage in mental state reasoning or Theory of Mind (ToM) differently across two fundamental social contexts: cooperation and competition. Study 1 examines how children with an emerging understanding of false beliefs deploy ToM across these contexts. We find that young preschool children are better able to plant false beliefs in others' minds in a cooperative versus competitive context; this difference does not emerge for other cognitive capacities tested (e.g., executive functioning, memory). Studies 2a and 2b reveal the same systematic difference in adults' ToM for cooperation and competition, even after accounting for relevant predictors (e.g., preference for a task condition; feelings about deception). Together, these findings provide initial evidence for enhanced ToM for cooperation versus competition in early development and also adulthood.


Low temperature combustion has proved to be beneficial for low NOx and particulate matter emissions. Renewable fuels, such as biodiesel, alcohol fuels, and ether fuels can further decrease the carbon footprint of the engine. The NO to NO2 ratio in engine out NOx emissions has shown dependency on the concentration of hydrocarbon emissions. This relationship has a significant impact on the design of exhaust after-treatment systems. However, the effect of the renewable fuels on NO to NO2 conversion process is less understood. This paper investigates the impact of DME and propane on the in-cylinder conversion of NO to NO2 in a compression ignition engine. Firing test under low temperature combustion condition is first performed to demonstrate the impact of HC concentration on exhaust NO concentration and composition. Then, motoring tests are performed with a mixture of the HC and NO dosed into the engine intake manifold. The simplified testing scenario makes it easier to understand HC-NO interaction. To simplify the process of understanding the difference in fuel behavior a study of NO to NO2 conversion as a resolution of engine cycle is conducted using a Gas Sampling Valve which is capable of collecting in-cylinder gases at varying crank-angles. The FTIR data from these compression tests can help assist future mechanism studies to be performed. This study aims to describe the impact of the two fuels on the NO to NO2 conversion process and the boundary conditions at which these differences occur.


In this paper we deal with the following problem: what are consequences of adopting the following property of Cantorian sets : ∀z(z is element of the set of all S-ses → z is an S) for mereological sets ? We show that the abovementioned principle does not hold for any notion of mereological set considered in literature. Further we prove that in case of some classical definitions of mereological set , enriching the theory of such sets with its counterpart leads to trivial, one-element theories. We also consider some less popular (but more natural) definition of mereological set in the form of the so called aggregate of objects and prove that in case of this adoption of the counterpart of the Cantorian principle reduces proper part of relation (i.e. one which is irreflexive) to set theoretical ∈. In the introduction we present an informal argument for some unwelcome consequences of adopting the principle for mereological sets as defined by means of mereological sums. In the sequel we are more formal and we turn to application of tools of mathematical logic to analyze the problem in its full scope.


A lateral top-heater phase-change memory (LTH-PCM) is proposed and investigated for multilevel storage (MLS). The active layers are composed of a 50-nm-thick TiN layer as a top heater and a 150-nm-thick SbTeN layer. A number of intermediate levels, which are induced by electric currents, are exhibited in experimental results. They are distinct and very stable. The reversible switching of multilevels is successfully demonstrated in the LTH-PCM device. The MLS results from the gradual enlargement of crystalline region between electrodes by Joule heating according to our analysis.


Distributed denial of service (DDoS) attacks have become a major threat to organizations and especially to Internet and intranet. In DDoS attacks targets are overwhelmed by sending an enormous amount of traffic from number of attack sites. The major tasks of any defense system are to detect these attacks accurately and early on, before it causes an unrecoverable loss. Most of the research in this regard has been focused on the detection techniques without exploiting spatial placement of detection system in a network. The ideal way to completely eliminate the DDoS threat is to run detection mechanism on every node in the network, which is not a practical solution. In this paper, we focus on the optimized placement of detection nodes in a network for distributed detection of DDoS attacks, which not only minimize the number of these node required but also reduce the cost, processing overheads and larger delays in identifying an attack. We examine the placement problem of finding a minimum cardinality set of nodes to detect DDoS attacks such that no attack traffic can reach the target without being monitored by these sensors. The placement problem is formulated as set covering which is NP hard.


Smart grid being a widely distributed engineering system may run through deep forests to long rivers, and over the cities as well. Physical damage to the power line from natural calamities or, cyber attacks by malicious people on the control system will hamper the functional integrity of the power grid. To ensure the usual operational flow, the control center needs to take immediate steps caused by these phenomena. Hence, inspection of the power line provides a means for the smart grid surveillance. Since any physical damage to the power network can be occurred in hardly reachable remote areas, understanding the amount of impairment will be time-consuming. Autonomous systems like Unmanned Aerial Vehicles (UAV), instead of the traditional human patrol, are one way to enable regular monitoring of the safety critical situations. The critical lines will be monitored by a fleet of UAVs to ensure a resilient surveillance system. In this work, we present a formal model for UAV surveillance resiliency over the power lines with a set of k UAVs from the whole set. The proposed approach at first considers the n-1 contingency analysis using actual system data, and state estimation procedures. By using linear sensitivity factors, we find the critical transmission lines in the smart grid and in accordance with that, placements and communication topology of the UAVs are done. Then, we evaluate k-resiliency for the UAV surveillance to cover all the critical lines satisfying the circumstances in case of k failure in the fleet of UAVs.


In recent years, face recognition has become one of the hottest research topics aimed at biometric applications. Comparing with other biometrics recognition, face recognition provides more natural means for perceptual interface. However, face recognition algorithms weakly perform under some common conditions, which include the variation of facial expressions or lightening conditions, the occlusion of faces like wearing glasses or mask, the low resolution or noises of input images, and the like. The other problem is the recognition efficiency, especially when the facial database is tremendous. This paper presents all common subsequences (ACS) as the kernel function (similarity method) to solve the time series problem. Experiments on 4 public face databases: Caltech, Jaffe, Orl and Yale databases, demonstrate that ACS can achieve higher recognition accuracy than some classic face recognition methods, e.g. 2DPCA and 2DLDA.These instructions give you basic guidelines for preparing camera-ready papers for conference proceedings.


Identifying positive success factors and addressing the factors that impede academic success for minority students in higher education, is a priority for most countries that are experiencing rapid population diversity. This qualitative study explored the experiences of first-year Pacific students at a New Zealand university, and undertook a comparative analysis of factors from two groups of students; one that successfully passed 50% of their first-year papers compared with those students who did not pass at least 50% of their academic papers. Students who succeeded in the first year of study used Pacific-centric student support services, had family members who had been to University before, and had different study habits, learning strategies and expectations from their peers who struggled to achieve. This study identified important aspects of the first-year transition for Pacific students, upon which tertiary institutions can have some impact. As first-year academic success predicts University completion, this study recommends further effort in first year transition interventions to address the social and academic adaptations that Pacific students need to make in order to be successful at University study.


Abstract We describe a new elasmobranch fauna from the lower part of the Khlong Min Formation in Thailand. The fauna includes Hybodus sp., Asteracanthus sp., Lonchidion reesunderwoodi sp. nov., Belemnobatis aominensis sp. nov., and possibly a second species of Belemnobatis. This fauna supports a Bathonian–Callovian age for the Khlong Min Formation, and suggests a close taxonomic relationship between the Middle Jurassic elasmobranch faunas of Europe and Thailand. The presence of a monolayered enameloid in Belemnobatis aominensis sp. nov. and other primitive batoids is interpreted as the retention of a primitive character for neoselachians, which would suggest a divergence time between the batoids and the rest of the neoselachian sharks as early as the Carboniferous–Permian boundary.


Abu Sa'id 'Abd al-Hayy Gardizi was an author and historian living in the mid-eleventh century at the height of the Turkish Ghazvanid dynasty. His only known work, "The Ornament of Histories" ("Zayn al-akhbir"), is a hugely ambitious history of the Eastern Islamic lands AD 650-1041, spanning what is now Eastern Iran, Afghanistan and parts of the Central Asian Republics and Indo-Pakistan subcontinent. Gardizi's text is an extremely rare source of primary information about the rise of Islamic faith, culture and military dominance in these regions, and represents a significant contribution to our understanding of the early Islamic world. This is the first English translation of the original Persian text, and is accompanied by an introduction and commentary which details the historical, geographical and cultural context.


Methods to estimate the amount of N mineralized from soil organic matter are needed for accurate fertilizer recommendations. We conducted laboratory and field studies to evaluate the method of Stanford and Smith for predicting N mineralized under field conditions. Soil samples were incubated to determine their N mineralization potentials and first-order rate constants of mineralization. To predict N mineralized in the field, the rate constants of mineralization were adjusted by soil temperature, and the amount of N mineralized predicted with the N mineralization potentials and adjusted rate constants were further adjusted by soil water content. Nitrogen mineralized in the field was measured in sorghum [Sorghum bicolor (L.) Moench] plots established on Haynie (coarse-silty, mixed, calcareous, mesic Mollic Udifluvent), Kahola (fine-silty, mixed, mesic Cumulic Hapludoll), and Richfield (fine, montmorillonitic, mesic Aridic Argiustoll) soils in 1983 and 1984. Nitrogen mineralized was also measured in fallow plots on Haynie and Wymore (fine, montmorillonitic, mesic Aquic Argiudoll) soils in 1984. The method only accurately predicted the amount of N mineralized in 104 d in fallow plots on Haynie soil. In all other cases, the method significantly overpredicted by 67 to 343% the amounts of N mineralized in the field. Among possible causes for the overpredictions may be an improper soil water content factor and the drying and sieving of the samples before incubation. Contribution no. 87-432-J from the Kansas Agric. Exp. Stn.


A young woman presenting with recurrent episodes of uterine bleeding due to an extensive uterine arteriovenous malformation was treated with two sessions of uterine artery embolization. Further bleeding was managed with a combination of gonadotropin-releasing hormone and depot medroxyprogesterone acetate. The patient remains asymptomatic with a significant decrease in uterine and pelvic vascularity at one year follow-up. These drugs may decrease the need for repeat embolization.


The modern naval air defense of a fleet is a critical task dictating the equipment, the operation, and the management of the fleet. Military modelers consider that an improved weapon system in naval air defense (i.e. the AEGIS system) is the most critical enabler of defense at the engagement level. However, at the mission execution level, naval air defense is a cooperative endeavor of humans and weapon systems. The weapon system and the command and control (C2) structure of a fleet engage in the situation through human reporting-in and commands, as well as weapon deployments. Hence, this paper models the combination of the human and the weapon systems in naval air defense by covering the C2 hierarchy of the fleet, as well as the weapon systems of warships. After developing this mission-level model, we perform battle experiments with varying parameters in the human and weapon aspects. These battle experiments inform us of the impact of the changes in the human and the weapon systems. For example, the speed of incoming missiles is a critical parameter for a fleet's survival; yet the decision-making speed is another outstanding parameter, which illustrates that there is more to improve than the weapon system when considering the mission level. This modeling and these experiments provide an example, suggesting a method of combining the human C2 and the weapon systems at the mission level in the military domain.


UNLABELLED
Well-publicized lapses in the review or implementation of clinical research studies have raised public questions about the integrity of the clinical research process. Public trust in the integrity of research is critical not only for funding and participation in clinical trials but also for confidence in the treatments that result from the trials. The questions raised by these unfortunate cases pose an important opportunity to reassess the clinical trials oversight system to ensure the integrity of clinical research and the safety of those who enroll in clinical trials. Since its inception, the American Society of Clinical Oncology (ASCO) has worked for the advancement of cancer treatments through clinical research and to help patients gain prompt access to scientifically excellent and ethically unimpeachable clinical trials. As an extension of its mission, ASCO is affirming with this policy statement the critical importance of a robust review and oversight system to ensure that clinical trials participants give fully informed consent and that their safety is a top priority. Ensuring the integrity of research cannot be stressed enough because of its seminal connection to the advancement of clinical cancer treatment. The overall goal of this policy is to enhance public trust in the cancer clinical trials process. To achieve this, the following elements are essential: 1. Ensure safety precautions for clinical trial participants and their fully informed consent. 2. Ensure the validity and integrity of scientific research. 3. Enhance the educational training of clinical scientists and research staff to ensure the highest standards of research conduct. 4. Promote accountability and responsibility among all those involved in clinical research (not just those serving on institutional review boards [IRBs], but also institutional officials, researchers, sponsors, and participants) and ensure support for an effective oversight process. 5. Enhance the professional and public understanding of clinical research oversight. 6. Enhance the efficiency and cost-effectiveness of the clinical research oversight system. This policy statement makes recommendations in several areas that serve as principles to support an improved system of oversight for clinical research. ASCO will work with all parties involved in the clinical research system to develop the steps necessary to implement these recommendations. Centralized Trial Review: A large percentage of oncology clinical trials are coordinated through the National Cancer Institute's (NCI) system of cooperative groups, which already incorporates centralized scientific review. As such, there is a tremendous opportunity to employ a centralized mechanism to provide ethical review by highly trained IRB members, allowing local IRBs to take advantage of the financial and time efficiencies that central review provides. Centralized review boards (CRBs) would also contribute consistency and efficiency to the process. Once successfully completed, the review would represent an approval to open the protocol at all of the institutions that have subscribed to the centralized review system. Local IRBs would be able to devote time usually spent on initial review to ongoing monitoring of the trial taking place at their institution. Considering the enormous size and complexity of the clinical research enterprise, ASCO envisions multiple CRBs, which could be distributed as regional review boards. Central review will use a single protocol and consent form, and monitor and evaluate adverse events (AEs) on a global basis, eliminating many of the time-consuming steps for the local IRB. Global monitoring and assessment of AEs has real potential to enhance trial participants' safety by giving local institutions more information on the overall trial and enabling them to devote more time to ongoing review of the trial onsite. Use of a CRB also has real potential to reduce the costs of clinical trial oversight by allowing local IRBs to eliminate the costs of initial review. These efficiencies will likely lead to institutions redirecting funds toward monitoring ongoing trials. Although a CRB has potential to improve the efficiency of the process, a CRB could also have tremendous ability to delay valuable trials. Checks and balances must be included in the newly devised system to ensure timely review and appeals of CRB actions. ASCO proposes the advent of a new pilot program for centralizing review of clinical trials. It requires clear engagement of all stakeholders in planning the experiment, clear articulation of the goals, and assurance of federal regulatory protection for institutions choosing to participate. If successful, this CRB pilot project could be expanded to include multi-institutional industry-sponsored research. Education and Training:Education and training are critical to the ultimate success of an improved oversight system. All members of the research team should receive comprehensive education on conducting scientifically and ethically valid clinical research. The curriculum should also include information on the prevailing local and federal regulations that pertain to the clinical trials process. IRB members should also receive ongoing education and training in the review of clinical research protocols. IRB training should pay particular attention to nonscientific members to give them the tools necessary to speak on behalf of research participants. ASCO should develop a curriculum that focuses on the proper conduct of human research and emphasize ethically sound clinical research in the context of its Annual Meeting. Informed Consent: Investigators and review boards have specific roles to play in ensuring the education of trial participants through the informed consent process, both when they are considering trial enrollment and as they participate in the trial. Review boards and investigators should focus primarily on the informed consent process, rather than the informed consent documents. Federal Oversight: The federal government has an important role to play in the oversight of clinical research. This role should be expanded to cover all research, not just that which is funded by the federal government or conducted with the oversight of the Food and Drug Administration (FDA). The Department of Health and Human Services (HHS) Office for Human Research Protections (OHRP) and the FDA should provide clear regulatory support and guidance for local institutions that choose to employ a CRB. In the case of the pilot CRB discussed in this policy statement, it should serve as the preferred option for the cancer cooperative group clinical trials. Ideally, the federal government should unify and streamline its regulations for the oversight of clinical research. Resources Supporting Clinical Research Infrastructure:An effective oversight process demands the highest quality scientific and ethical review and onsite monitoring of the safety of trial participants. This can only be accomplished by the involvement of an experienced IRB that receives funding, resources, and institutional support enabling it to fulfill its mandate.

CONFLICT OF INTEREST
Critical to the integrity of research is the absence of bias in the process. ASCO strongly recommends the adoption of standards for the identification, management, and, where appropriate, elimination of conflicts of interests, whether they are actual, potential, or apparent.


Products of large-N conformal field theories coupled by multi-trace interactions in diverse dimensions are used to define quantum multi-gravity (multi-string theory) on a union of (asymptotically) AdS spaces. One-loop effects generate a small O(1=N) mass for some of the gravitons. The boundary gauge theory and the AdS/CFT correspondence are used as guiding principles to study and draw conclusions on some of the well known problems of massive gravity – classical instabilities and strong coupling effects. We find examples of stable multi-graviton theories where the usual strong coupling effects of the scalar mode of the graviton are suppressed. Our examples require a fine tuning of the boundary conditions in AdS. Without it, the spacetime background backreacts in order to erase the effects of the graviton mass.


ABSTRACT Few data exist on the clinical utility of the expanded-spectrum tetracyclines doxycycline and minocycline for the treatment of community-associated methicillin-resistant Staphylococcus aureus (MRSA) skin and soft tissue infections (SSTI). We performed a retrospective cohort study of 276 patients who presented with 282 episodes of MRSA SSTI to the emergency room or outpatient clinic at two tertiary medical centers between October 2002 and February 2007. The median percentage of patients infected with MRSA strains that were susceptible to tetracycline was 95%. Time zero was defined as the time of the first incision and drainage procedure or, if none was performed, the time of the first positive wound culture. The median patient age was 48 years. Abscesses constituted the majority of clinical presentations (75%), followed by furuncles or carbuncles (13%) and cellulitis originating from a purulent focus of infection (12%). A total of 225 patients (80%) underwent incision and drainage. Doxycycline or minocycline was administered in 90 episodes (32%); the other 192 SSTI were treated with β-lactams. Treatment failure, defined as the need for a second incision and drainage procedure and/or admission to the hospital within at least 2 days after time zero, was diagnosed in 28 episodes (10%) at a median of 3 days after time zero. On logistic regression analysis, receipt of a β-lactam agent was the only clinical characteristic associated with treatment failure (adjusted odds ratio, 3.94; 95% confidence interval, 1.28 to 12.15; P = 0.02). The expanded-spectrum tetracyclines appear to be a reasonable oral treatment option for patients with community onset MRSA SSTI in areas where MRSA strains are susceptible to the tetracyclines.


This thesis was conducted in the field of Environmental technology for the Sustainability & Technology Assessment group, at Singapore Institute of Manufacturing Technology. Singapore Institute of Manufacturing Technology is a research institute, striving to contribute to Singapore's industrial capital through use-inspired research. The manufacturing industry contributes to a significant portion of the world´s total energy and resource consumption. This resource consumption could be reduced significantly through sustainable initiatives and technologies already available today. The reasons why companies choose not to invest in such technologies are often not due to technical factors, but rather due to financial factors. Financial barriers exist because investments are made on the basis of cost based value systems, which seldom justify investments in sustainable technology. When investments are made, the primary reason is to reduce costs while intangible benefits are ignored. However, this study shows that sustainability creates intangible value that current value systems cannot account for. Understanding the true value of sustainability would help decision makers realize that sustainable manufacturing is a viable business opportunity. This thesis studies the effect sustainable attributes has on a company's ability to generate value. A value system is proposed, linking 40 sustainable attributes to value domains of intangible value. The value of sustainable attributes is quantified using the Sustainable Value approach. The study shows that social indicators, deemed by others to be unsuitable, can be used when proper adjustments to the Sustainable Value approach are made. A case study was performed on the Swedish manufacturing company Finess Hygiene AB to investigate the applicability of the model. The case study showed that the value system was applicable using data that already exists within the company, but the main challenge lies in collecting good and reliable benchmark data. Benchmark data is significantly easier to obtain in Sweden than Singapore for users wishing to apply the proposed value system. A follow up study should be performed to study the potential of a large scale adoption of the value system in Singapore.


This paper investigates the impact of pedestrian environments on walking behavior, and the related choice of travel path for transit riders. Activity logs from trip surveys combined with transit-route and land-use information are used to fit discrete-choice models of how riders choose among multiple paths to downtown destinations. The work illustrates (1) how the quality of pedestrian environments along transit egress paths affects transfers inside a transit system, and (2) how the impedance of transferring affects egress walking path choices. The use of GIS techniques for path-based spatial analysis is key to understanding the impact of pedestrian environments on walking behavior at the street level. The results show that desirable pedestrian environments encourage transit riders to choose paths that are 'friendlier', even if they involve more walking after leaving transit. Policy implications for land-use planning and transit service planning are discussed.


This paper, written in the Dutch language analyzes the territorial scope of application of different branches of EC and EU law and the applicability of the concept of territoriality to European law. A special emphasis is put on the analysis of the applicability of EU and EC law in the territories possessing two main special statuses under Art. 299 EC: Ultra-peripheral regions (in the sense of Art. 299(2) EC) and overseas countries and territories associated with the Community (in the sense of Art. 299(3) EC and Annex II EC). The paper does not only focus on the legal essence of both special statuses and the dynamics of their recent evolution, but also contains detailed assessment of the procedural requirements for territories' status change in EC law, including the new procedures to be introduced upon the entry into force of the Treaty of Lisbon. Special attention is paid to the nature and the extent of possible derogations from the acquis communautaire to be enjoyed by the ultra-peripheral regions.This paper is a chapter of the report 'Schurende rechtsordes: Over juridische implicaties van de UPG-status voor de eilandgebieden van de Nederlandse Antillen en Aruba' on the analysis of the legal implications of the possible ultra-peripheral region status for the Netherlands Antilles and Aruba, commissioned by the Netherlands Ministry of Interior and Kingdom Relations, prepared by the Research School of the Faculty of Law, Groningen University and edited by H.E. Broering, D. Kochenov, H.G. Hoogers and J.H. Jans.


ABSTRACT: We examine dominant ownership in Continental European firms to further refine the distinction between the ability to control and actual control and whether a particular distinct shareholder ownership type is associated with company performance. In addition, we empirically test whether the economic performance of the firms from different countries is consistently affected by the nature of the company's dominant owner. After disaggregating the overall sample by specific ownership type and by country, we find a positive relationship between dominant ownership and performance for firms in which banks and families/individuals are the dominant owners and a negative relationship when corporations are the dominant owners. Additional analysis discloses an even more complicated picture, suggesting that countries are not homogenous in terms of their ownership landscapes and, hence, their effects on performance.


In a recent paper, A.Valentini tried to obtain Born's principle as a result of a subquantum heat death, using classical H-theorem and the definition of a proper quantum H-theorem within the framwork of Bohm's theory. In this paper, we shall show the possibility of solving the problem of action-reaction asymmetry present in Bohm's theory by modifying Valentini's procedure. However, we get his main result too.


Information systems (IS) investments fail largely because a newly implemented system is not fully infused into its users' everyday life at work. IS infusion beyond an organization's mandated usage requires that users are actively motivated to use it and that they hold authority over usage of the system. Psychological empowerment represents one's motivational orientation, as well as one's authority to tap into a system's maximum potential. This empowerment is likely an important mechanism underlying successful IS infusion. The main objectives of this study are to: 1) understand the antecedents of empowerment; and 2) examine the effect of empowerment on IS infusion. We developed a theoretical model that was empirically tested through a field study, which focused upon individuals' use of a customer relationship management system. The results strongly support our theoretical model and reveal that the design of a work environment (i.e., IS, job, and social structure) affects the development of user empowerment. User empowerment in-turn plays a prominent role in regulating various aspects of IS infusion (i.e., extended use, integrative use, and emergent use). Overall, this paper contributes to postadoption research by introducing the concept of user empowerment and demonstrating its critical role in regulating IS infusion. It also helps managers promote user empowerment and eventually achieve IS infusion in organizations.


In this study we derive a mathematically rigorous kernel function, which accounts for the interaction among particles, within the framework of the particle method, to predict a computationally more accurate solution for the convection-diffusion equation investigated at low as well as high Peclet numbers. Determination of the functional dependence of the kernel function on the distance vector between the particles is therefore a key to the success of the interaction model. The smoothed quantity for a scalar or for a vector at a particle location is mathematically identical to its collocated value provided that the kernel function is chosen as the delta function. Such a kernel is unfortunately not computable in a discrete context. Our guideline for developing the modified kernel function is therefore to make it closer to the delta function as much as possible in cases when diffusion dominates convection. To achieve this goal, we enforce five constraint conditions in a derivation of the kernel function for the pure diffusion equation. In addition, this kernel function has no effect on the particles outside of the disk, which has the user's specified radius r e . To mimic the delta function we demand that the developed kernel function at r = r e should smoothly approach zero. It is also desired to acquire the largest possible value for the kernel function near r = 0. As flow convection prevailingly dominates its diffusion counterpart, particle interaction at the upstream side should be more favorably taken into account to avoid numerical oscillations due to convective instability. We present in this study a two-dimensional upwind kernel function to enhance numerical stability along the flow direction. The proposed upwind kernel function can render an exact solution for the investigated convection-diffusion equation in the limiting one-dimensional case. The proposed particle interaction model featuring the newly developed kernel function is validated through several problems that are amenable to analytical solutions or have available benchmark solutions. Analysis of the stability condition and spatial accuracy order of the proposed particle interaction model are also provided in details.


Country women and the colour bar is a timely corrective to established ideas about race relations in rural New South Wales by revealing the untold story of grassroots efforts by Aboriginal and white women, working together.In the 1950s and 1960s, in towns across New South Wales, Aboriginal women joined specially created Aboriginal branches of the Country Women's Association. Country women and the colour bar offers insights into the experience of ordinary Aboriginal and white rural women as they participated in beauty contests, cookery, handicraft lessons and baby contests. It reveals how Aboriginal assimilation policy met everyday reality as these rural women broke with the established segregation in an unprecedented fashion. Working together the women made significant gains for Aboriginal communities prior to Aboriginal people's widespread access to citizen's rights. Some prominent Australians feature in these extraordinary stories: Jessie Street, Charles Perkins, Rachel Mundine and Purth Moorhouse. Using a biographical and highly accessible approach, Country women and the colour bar is an exploration of the role of women in maintaining and challenging the colour bar.


This paper provides an overview of the theory and methods used to implement use-value property tax assessment for agricultural land in the United States. After a critical review of the methods used by various states in their application of use-value statutes for agricultural land, the paper examines several policy issues related to the estimation and application of use-value assessment methods. Five state case studies are included, providing an overview of methods used in use-value assessment, and suggestions are provided regarding several ways in which use-value assessment methods need to be improved.


Binaural audio plays a significant role in constructing immersive augmented and virtual realities. As it is expensive to record binaural audio from the real world, synthesizing them from mono audio has attracted increasing attention. This synthesis process involves not only the basic physical warping of the mono audio, but also room reverberations and head/ear related filtrations, which, however, are difficult to accurately simulate in traditional digital signal processing. In this paper, we formulate the synthesis process from a different perspective by decomposing the binaural audio into a common part that shared by the left and right channels as well as a specific part that differs in each channel. Accordingly, we propose BinauralGrad, a novel two-stage framework equipped with diffusion models to synthesize them respectively. Specifically, in the first stage, the common information of the binaural audio is generated with a single-channel diffusion model conditioned on the mono audio, based on which the binaural audio is generated by a two-channel diffusion model in the second stage. Combining this novel perspective of two-stage synthesis with advanced generative models (i.e., the diffusion models),the proposed BinauralGrad is able to generate accurate and high-fidelity binaural audio samples. Experiment results show that on a benchmark dataset, BinauralGrad outperforms the existing baselines by a large margin in terms of both object and subject evaluation metrics (Wave L2: 0.128 vs. 0.157, MOS: 3.80 vs. 3.61). The generated audio samples (https://speechresearch.github.io/binauralgrad) and code (https://github.com/microsoft/NeuralSpeech/tree/master/BinauralGrad) are available online.


We investigate the electronic structure of Nickel sulphide (NiS) in the millerite phase using electron spectroscopic measurements and band structure as well as model Hamiltonian calculations. While band structure calculations are found to be relatively more successful in describing the experimental valence band spectrum of this highly conducting phase compared to the hexagonal phase of NiS, cluster calculations including electron correlation effects are found to be necessary for the description of certain features in the experimental spectra, indicating the importance of correlation effects even in a highly metallic system. The electronic parameter strengths obtained from these calculations confirm that the millerite NiS is a highly covalent pd metal. The comparative study of hexagonal and millerite forms of NiS, provides the information concerning the evolution of the spectral function in a pd metal as a function of covalency.


Introduction: Though there is currently no approved treatment for COVID-19, potential medications include lopinavir and doxycycline. Lopinavir is a broad-spectrum protease inhibitor successfully used during the SARS outbreak. Doxycycline is an antibiotic with immunomodulatory effects, which successfully treats dengue hemorrhagic fever. Comparing lopinavir combined with doxycycline with other commonly implemented COVID-19 treatment regimens is of medical significance. Methods: We conducted a retrospective study comparing two cohorts. One cohort strictly adhered to a treatment protocol of lopinavir combined with doxycycline (Lop/Dox), while the other cohort (Others) applied protocols based on combinations of favipiravir, hydroxychloroquine, and azithromycin. The outcomes evaluated were death from coronavirus and intubation. Results: During the study period, 161 and 114 patients were followed in the Lop/Dox cohort and the Others cohort, respectively. The Lop/Dox cohort was older and had lower O2 saturation at admission. The proportion of patients needing intubation did not differ between the cohorts (Lop/Dox, 15∙5%; Others, 16∙7%). The overall fatality rate likewise did not differ (12∙4%) in Lop/Dox and 8∙7% in the Others cohort). Older age and elapsed time between the onset of symptoms and hospitalization, O2 saturation at admission, and the lymphocyte to white blood cell ratio were independent risk factors for poor outcomes of the illness. Conclusion: This study showed that lopinavir plus doxycycline therapy is an effective treatment amongst moderate to severe COVID-19 patients.


We report on the efficient high-power operation of a laser-diode-pumped Er3+-doped yttrium aluminum perovskite (Er:YAP) laser in the 3 μm spectral region at room temperature. 6.9 W of continuous-wave (CW) output power was obtained at 2920 nm. The slope efficiency was as high as 30.6% with respect to the absorbed pump power, which is close to the quantum defect limit (33.4%). To the best of our knowledge, this is the highest CW output power generated from 3 μm Er3+-doped solid state lasers at room temperature. Furthermore, our analysis has shown that more than 10 W of output power based on Er:YAP is possible by further mitigating the thermal lens effect.


Rheumatoid arthritis (RA) is a chronic autoimmune disease, affecting up to 1% of the UK population. It is thought that RA is the result of several genetic and environmental susceptibility factors, which in combination can result in disease manifestation. Overall it is estimated that genetic factors contribute 50% of disease risk, indicating a greater understanding of this component is essential.

Although genetic studies have been performed for several years, a greater understanding of human genetics, combined with advances in molecular technology has revolutionised the identification of RA-associated genes. To date 34 susceptibility loci have been identified, including many immune genes indicating that immune disparity may have a great role to play in RA pathogenesis.

With several potential associations in the pipeline, future challenges focus on the identification of biological functions of susceptibility genes. These discoveries will provide crucial information for unravelling the pathogenic disease networks and elucidating potential targets for novel RA therapies.

Key Concepts:

Rheumatoid arthritis has a significant genetic contribution to risk.

Recent advances have identified a number of genes or genomic regions associated with disease risk.

Keywords:

rheumatoid arthritis;
genetics;
GWA studies;
HLA;
PTPN22


We have studied the effect of deviations from doping uniformity in source and drain on the performance of sub-20 nm silicon double-gate MOSFET devices. The study is motivated by recent direct observation of such inhomogeneities in small MOSFET devices. The model assumes a continuous charge distribution with randomly located regions of high doping. Individual dopants are not resolved. Impurity scattering in the source and drain regions is neglected. The current-voltage characteristics are computed for devices that differ only in the microscopic arrangement of the randomly distributed high doping regions. We have also studied devices that differ in the number of these clusters. An ensemble of devices with fluctuating numbers of clusters has been constructed based on a Gaussian distribution centered on the mean cluster number derived from the average doping concentration in the source/drain. The impact of high doping clusters, particularly on charge injection, has been studied in detail for the first time using full quantum simulation based on the 2D nonequilibrium Green function approach coupled self-consistently to Poisson's equation. We have assumed an average lateral symmetry for the double-gate MOSFET. Therefore, we only consider inhomogeneities in doping in the plane of the simulation. The devices studied have 12 nm channel lengths which allows the approximation of ballistic quantum transport through the self-consistent electrostatic potential landscape of the device. The computed current-voltage characteristics are monotonic and they are most strongly affected by the fluctuations in the total number of high doping regions. Fluctuations in the spatial configuration of clusters have a lesser effect. Threshold voltages shifts around 100 mV and on-current fluctuations around 50% are obtained from the simulations. However, the subthreshold slope remains almost independent of the microscopic cluster distribution. The on-current variations are considerably larger than those predicted from classical modeling.


Sterile neutrinos, if they exist, are potential harbingers for physics beyond the Standard Model. They have the capacity to shed light on our flavor sector, grand unification frameworks, dark matter sector and origins of baryon anti-baryon asymmetry. There have been a few seminal studies that have broached the subject of sterile neutrinos with low, electroweak-scale masses (i.e. $\Lambda_{\text{\tiny{QCD}}} \ll m_{N_R} \ll m_{W^\pm}$) and investigated their reach at hadron colliders using lepton jets. These preliminary studies nevertheless assume background-free scenarios after certain selection criteria which are overly optimistic and untenable in realistic situations. These lead to incorrect projections. The unique signal topology and challenging hadronic environment also make this mass-scale regime ripe for a careful investigation. With the above motivations, we attempt to perform the first systematic study of low, electroweak-scale, right-handed neutrinos at hadron colliders, in this unique signal topology. There are currently no active searches at hadron colliders for sterile neutrino states in this mass range, and we frame the study in the context of the $13\,\rm{TeV}$ high-luminosity Large Hadron Collider and the proposed FCC-hh/SppC $100\,\rm{TeV}$ $pp$-collider.


In atherosclerotic lesions, the endothelial barrier against the bloodstream can become compromised, resulting in the exposure of the extracellular matrix (ECM) and intimal cells beneath. In theory, this allows adequately sized nanocarriers in circulation to infiltrate into the intimal lesion intravascularly. We sought to evaluate this possibility using rat carotid arteries with induced neointima. Cy5-labeled polyethylene glycol-conjugated polyion complex (PIC) micelles and vesicles, with diameters of 40, 100, or 200 nm (PICs-40, PICs-100, and PICs-200, respectively) were intravenously administered to rats after injury to the carotid artery using a balloon catheter. High accumulation and long retention of PICs-40 in the induced neointima was confirmed by in vivo imaging, while the accumulation of PICs-100 and PICs-200 was limited, indicating that the size of nanocarriers is a crucial factor for efficient delivery. Furthermore, epirubicin-incorporated polymeric micelles with a diameter similar to that of PICs-40 showed significant curative effects in rats with induced neointima, in terms of lesion size and cell number. Specific and effective drug delivery to pre-existing neointimal lesions was demonstrated with adequate size control of the nanocarriers. We consider that this nanocarrier-based drug delivery system could be utilized for the treatment of atherosclerosis.


The underlying managerial rationale for segmenting markets is well established, with the marketing literature citing a range of benefits for businesses adopting a segmentation approach. Yet organisations frequently encounter difficulties in implementing segmentation principles. Even in the industrial marketing literature, where the most practical implementation guidance is offered, it is suggested that organisations tend to over‐emphasise the mechanics of segmentation, while failing to correctly implement the findings. This suggests that, if organisations are to benefit from applying segmentation principles, two fundamental questions should be addressed. The first concerns the basic conditions which must be met if implementation is to be effected. That is, it must be possible to map the dimensions developed on to usable customer characteristics. The second concerns the costs and benefits of the segmentation solution in relation to the proportion of variance in customer requirements which it explains. Addresses these questions in an industrial marketing context, using a literature review and quantitative analysis of data from the European car parts after market. The analysis shows that whilst traditional segmentation methods can be used to identify certain segments, these segments do not readily map on to implementable dimensions. Furthermore, it is suggested that even a relatively wide use of structural independent variables explains only a very small proportion of the individual variability in customer requirements. This suggests that much segmentation analysis may be poorly directed and also of rather limited practical value.


Compressive experiments and finite element method (FEM) have been used to study the mechanical behavior of composite laminate with plies drop-off. A user subroutine has been implemented to ABAQUS to simulate the damage development of the laminate plate. This user subroutine has taken consideration of the mechanical properties degradation according to development of three types of damage. The load-strain curves can agree with each other between experiments and FEM. The detail of damage development of the plies drop-off composite laminate under compressive loading can be described as followed. Matrix cracking damage and fiber-matrix shearing damage occur simultaneously at first, and then fiber buckling damage initiates. Matrix cracking and fiber-matrix shearing are very dangerous to the carrying capacity of laminate and fiber buckling intensifies further this effect. The initiation and development of fiber buckling indicates that laminate loses carrying capacity at all.


Wavelet decomposition problems have been modeled as linear programs - but only as extremely dense problems. Both revised simplex and interior point methods have difficulty with dense linear programs. The question then is how to get around that issue. In our experiments the standard method outperforms a revised implementation for these problems. Moreover, the standard method can be easily and scalably distributed. Hence the standard simplex method should be useful in solving wavelet decomposition problems.


Yeast is starting to be looked at as a potential biofuel. If yeast is to become the next major fuel source we will need a large amount of yeast in the most efficient way possible which means that researchers must determine the optimal conditions for yeast production. We were interested in determining if pH affects yeast growth and what pH would produce the most yeast. We decided to test the acidic pH range because we found a few studies that suggested that yeast grew better in acidic environments. We used vinegar to lower our pH and tested a pH of 4, a pH of 5.3, and a neutral pH of 7.5 as our control. We collected our data by recording CO2 ppm for 5 minutes and finding the slope of the line using the Logger Pro. We conducted two trials and found that the environment of 5.3 produced the most yeast. Future studies should use more reliable equipment and conduct more trials to find a more accurate trend.


In this paper we describe a real time facial features tracker applied to the detection of some basic drowsiness behaviours in drivers, with a colour camera. It uses stochastic colour segmentation to robustly track a person's skin and some facial features (eyes and lips).The system recovers 3D face direction, classifies rotation in all viewing directions and detects the driver's state analysing eye blinking and face direction. We show some experimental results, using real sequences with several users, and some conclusions about the performance of the system. Key-Words: Facial Features Tracking, Driver Drowsiness, Colour Segmentation, 3D Recover, Eye Blinking.


Objective: to establish the features of the immune response in the early stages of diffuse toxic damage. Materials and methods. Diffuse toxic liver damage of male Wistar rats was caused by a single intraperitoneal injection of an oil solution of carbon tetrachloride (CCl4) at a dose of 50 mg/100 g. Animals were carried out from the experiment on days 3, 7 and 14. The study included hematological and histological analysis, immunohistochemical (IHC) staining of liver, thymus and spleen tissues, quantitative evaluation of CD3+, CD45RA+ (T-and B-lymphocytes), F4/80+ (macrophages), and HSP70+-cells. Results. CCl4 administration has been shown to cause structural disorders of liver, thymus, and spleen tissue. In the early stages, there is an increase in CD3+-cells in the liver and spleen, while CD45RA+-cells predominating in the thymus. On the 3rd day after CCl4 administration, the number of F4/80+-cells in the liver increases by 56.7%, in the thymus and spleen by 21% and 19.3%, respectively, there is also an increase in the number of HSP70+-cells roughly 2 times in the liver and thymus, and by 7 times in the spleen. Conclusion. Hepatotropic poison CCl4 causes damage not only the liver but the organs of immunopoesis. In the early stages of exposure to the toxicant the predominant population is T-lymphocytes (CD3+-cells) in the liver and spleen, and B – lymphocytes (CD45RA+-cells) in the thymus. In all the studied organs, the number of macrophages increases on the 3rd day of the experiment, and significantly decreases at the later term. This fact indicates that macrophages act as a target of toxic effects. The increase in the number of HSP70+-cells in the liver, thymus, and spleen in response to toxic damage is likely aimed at triggering the repair or elimination of denatured proteins that are toxic to the cell.


The course of spinal muscular atrophy (SMA) is not well established except for those patients whose age of onset is before 6 months and who achieve only "sit with support" as their maximum function (Werdnig-Hoffmann disease or SMA I). This study shows that there is another group of SMA patients whose age of onset and maximum function achieved can be used as prognostic guides. Fifty percent of SMA patients who could walk without assistance and whose onset was prior to age 2 years lost the ability to walk independently by age 12. Fifty percent of SMA patients who walked and whose onset was between 2 and 6 years of age lost walking ability by age 44 years. Fifty percent of SMA patients who could walk with assistance as their best function ever achieved lost this ability by age 7 years, unrelated to age of onset; none could walk with assistance after age 14 years. Seventy-five percent of SMA patients who developed the ability to sit independently as their best function were still sitting after age 7 years independent of age of onset; 50% of this group could sit independently after age 14 years. Eighty-five percent of SMA patients who could walk could not negotiate stairs without holding onto a rail. They could raise their hands above the head; however, as they lost walking ability, they lost this function as well. Only one SMA patient whose maximum function was sitting independently could get to the sitting position on his own. Only two of these patients could hold their hands above their heads. All patients with SMA lose function over time. This function loss occurs slowly and is related primarily to maximum function achieved; knowledge of age of onset provides helpful information, especially for predicting the loss of independent walking. NEUROLOGY 1996;47: 973-976


Guided by existing macrolevel theories on punishment and society, the present study explores the independent and conjunctive effects of measures of sociopolitical conditions on the legal retention of capital punishment in 185 nations in the 21st century. Significant correlations are found between a nation's retention of legal executions for ordinary crimes and its level of economic development, primary religious orientation, citizens' voice in governance, political stability, and recent history of extrajudicial executions. Subsequent multivariate analyses through qualitative comparative methods reveal substantial context-specific effects and wide variability in legal retention even within countries with similar sociopolitical structures. These results are then discussed in terms of their theoretical implications for future cross-national research on punishment and society.


Group testing has been used in many applications to efficiently identify rare events in a large population. In this paper, the concept of group testing is generalized to applications with correlated source models to derive scheduling policies for sensors' adopting cooperative transmissions. The tenet of our work is that in a wireless sensor network it is advantageous to allocate the same channel dimensions to all sensor sources that have the same response to a sequence of queries or tests. That is, nodes that have the same data attributes should transmit as a cooperative super-source. Specifically, we consider the case where sensors' data are modeled spatially as a one-dimensional Markov chain. Two strategies are considered: the recursive algorithm and the tree-based algorithm. The recursive scheme allows us to illustrate the performance of group testing for finite populations while the tree-based algorithm is used to derive the achievable scaling performances of the class of group testing strategies as the number of sensors increases. We show that the total number of queries required to gather all sensors' data scales in the order of the joint entropy. A further generalization of this concept provides the basis of deriving efficient data-gathering algorithms for correlated sources.


Research of this final Duty executed regional Public Bank region Indonesia Bank (BI) with title ANALYSE LEVEL OF REQUEST INVESTMENT CREDIT AT PUBLIC BANK IN]REGION WORK INDONESIAN BANK (BI) MALANG and this research have the character of deskritif qualitative. As for problem formulated in this research first is, How big the influence mount rate of interest of investment credit and inflation rate to request of investment credit at Public Bank in region Work Indonesian Bank (BI) Malang. Second, Where of among the variable having an effect on dominant to request of investment credit at Public Bank in region work Indonesian Bank (BI) Malang. In this research use data of sekunder which have been publicized by Indonesia Bank (BI) where of analyzer of data used is double linear regresi by using program eviews, where solution focussed at growth of investment credit at Public Bank in region work Indonesian Bank (BI) Malang. From result analyse obtained [by] that really from second of variable used in this model, channeling of Investment Credit still very base on level of rate of interest of credit and inflation. For a while from test conducted by pursuant to hypothesizing test, obtained by that from second of free variable really have an effect on do not significan of except variable mount rate of interest of investment credit to storey;level of request of investment credit . As for result from tester by using the following inferential classic assumption: Request of investment credit at Public Bank in region work Indonesian Bank (BI) of improvement. Where if level of rate of interest of Tur?n hence mount request of investment credit will go up, conversely. Thereby the researcher give suggestion to maker of policy in order to the effort government specially in giving amenity of channeling of investment credit of banking in society very expected by entrepreneur or client of banking to in this time. Because a period of Now along with global crisis all entrepreneur require amenity in getting credit of banking specially credit of working capital for improvement in course of production and also promotion Keyword : kredit investasi


The origins of the housebreaking crime (for the sake of brevity this term will be used throughout this note, rather than the bulkier (but more accurate) "housebreaking with the intent to commit a crime") are inexorably bound up with the need to protect the dweller in his or her abode. From the earliest times the interest of a person in the safe and private habitation of his home has been treated reverently and regarded as deserving of special protection by the law. This concern is reflected by the fact that common-law jurisdictions have typically classified housebreaking as a crime against the habitation, which implies the right to "feel secure in one's own home". With the broadening of the ambit of the crime (variously referred to as burglary or breaking and entering in other jurisdictions) beyond merely protecting habitation, differing approaches have been taken in defining the nature of the premises that can be broken into. Thus in English law, to be a "building" within the definition of the crime (in terms of s 9(1) of the Theft Act, 1968) the structure is required to have some degree of permanence and an inhabited vehicle or vessel is specifically included in theterm "building" (s 9(4) of the Theft Act, 1968). In Canada, breaking and entering (in terms of s 348 of the Canadian Criminal Code, RSC 1985, c.C-46) include, within the understanding of a "structure" which can be broken into and entered, spaces enclosed by a fence, but not unenclosed spaces. The position in South Africa has not been definitively resolved, although it can at least be accepted that it is incorrect to state that the breaking into and entering can only be in respect of an immovable structure, and cannot be committed by breaking into a movable structure. What then is the South African position regarding the nature of a "premises" which is protected by the housebreaking crime?


Orbital Decay in Triaxial Shaped Dark Matter Haloes by Ja lp esh Sachania In cosmological simulations of structure formation of the universe, the dark m atter halos in which galaxies are embedded in, are triaxial in shape. Simulations which focus in on galaxies in isolation do not use triaxial dark m atter halos but use spherical shaped halos instead, as triaxial equilibrium models are hard to create. Using a new method of creating initial conditions, which is able to create triaxial equilibrium models, the effect of using a triaxial halo in simulations of satellite accretion will be studied. In previous studies with a spherical shaped dark m atter halo, the initial position of the satellite is unim portant due to the symmetry of the system, however in a triaxial halo this is not the case and the initial position becomes im portant. A study of the parameter space of the initial position and velocity of a satellite is undertaken and the orbital decay is compared in each case. The different mergers will also have different effects upon the halo itself as the orbital energy of the satellite is transferred to the halo. The effects of a minor merger onto the halo is investigated and compared to the scenario more commonly used when the halo is spherical. This study is then extended to find out whether the orbital decay in a triaxial potential, which can differ significantly from th a t in a spherical halo, can be used to explain the observations of polar ring galaxies and gas discs in elliptical galaxies.


Since few years the electric vehicles draw the attention. The battery technology's continual improvements and incentives from the authorities guarantee them an assured future with a fast and considerable development. Some figures are forecasted by 2020: one or two millions electric vehicles. This could mean a huge increase in electricity consumption. The consequences on the total energy consumption have already been analyzed, however studies on the impact on the load curve remain scarce. In this context, this master thesis focuses on the impact of the electric vehicles' charge on the French load curve and the production and consumption balancing. The grid issues are not studied here.The first part presents the state of the art in battery and electric vehicle technology, as well as battery charge's characteristics. Besides the French traffic data are studied, in order to build the most realistic model as possible.The second part explains the principle of the modeling. A general and flexible model for the French fleet is built. This model can simulate the times of charge of a vehicle, and the state of charge of its battery, in order to get a total load curve for several days for an electric fleet. And finally, the different load curves are analyzed as well as their impacts on the electric balancing system and the possible solutions to lower these impacts. As the peak load for the electric vehicles' charge corresponds to the total consumption peak in the evening according to the most probable scenario, services have to be implemented to reduce or put back the overload due to the electric vehicles. Those services (tariff signals regulations, battery management system, cut-off injunctions) have been tested. A model for grid injections during peak hours has also been developed, in order to help the electric system, and erase the electric vehicles' impact on the load curve. Studies for the optimum load, the reserves and the margins are also suggested as well as other possible studies, such as EV's carbon footprint. The reflections and strategies developed in this master thesis don't reflect RTE's policy and don't commit the company.


We describe a data analysis method using a structure adapting neural network with two additional layers. The neural network used is an extended version of a self-organising feature map which can adapt its structure to better represent the clusters in data. Once the clusters are identified, we use two additional layers on the feature map to analyse the clusters and the representation of attributes in the clusters. Simulations and initial results with two simple benchmark data sets are also described.


Background. Interleukin (IL)-21 is the most recently described cytokine that signals via the common cytokine receptor (γc), is produced by activated CD4+ T-cells, and regulates expansion and effector function of CD8+ T-cells. Materials. To explore the actions of IL-21 with other γc-dependent cytokines in alloreactivity, mRNA expression of IL-21, IL-21R α-chain, and IL-2 proliferation and cytotoxicity was measured after stimulation in mixed lymphocyte reactions. Additionally, IL-21 and IL-21R α-chain expression was studied in biopsies of heart transplant patients. Results. Analysis of mRNA expression levels of allostimulated T-cells showed a 10-fold induction of IL-21 and IL-21R α-chain. Interestingly, induction of IL-21 was highly dependent on IL-2 (as in the presence of anti-IL-2, anti-IL-2R α-chain, and the immunosuppressive drugs cyclosporine A, tacrolimus, and rapamycin) the transcription of IL-21 was almost completely inhibited, whereas in the presence of exogenous IL-2 the mRNA expression of IL-21 was even more upregulated. IL-21 functioned as a costimulator for IL-2 to augment proliferation and cytotoxic responses, while blockade of the IL-2 route abrogated these functions of IL-21. Blockade of the IL-21 route by anti-IL-21R α-chain monoclonal antibodies inhibited the proliferation of alloactivated T-cells. Also, in vivo alloreactivity was associated with IL-21/IL-21R α-chain expression. After heart transplantation, the highest intragraft IL-21, IL-21R α-chain, and IL-2 mRNA expression levels were measured during acute rejection (P<0.001, P=0.01, P=0.03). Conclusion. IL-21 is a critical cytokine for IL-2 dependent immune processes. Blockade of the IL-21 pathway may provide a new perspective for the treatment of allogeneic responses in patients after transplantation.


: Muscular relaxant vecuronium bromide (Norcuron R, Organon Teknika Espanola, S.A.) was administered to 20 patients undergoing intracranial surgery with general anesthesia at a dose of 0.01 mg/kg weight followed by 0.1 mg/kg (intubation dose) four minutes later. Two minutes after the second dose and under careful manual mechanical ventilation with O2 100%, a laryngoscopy was performed to evaluate the conditions for intubation. Mean arterial pressure, heart rate, PaO2, and PaCO2 were measured at baseline and immediately before laryngoscopy. Neuromuscular function was monitored observing the response to a train of four stimuli applied on the cubital nerve. During the operation a continuous infusion of vecuronium at a rate of 1 microgram/kg/min was maintained. Conditions for intubation were excellent in 18 patients and good in two cases. Mean heart rate and PaCO2 did not show significant variations. In contrast, during prelaryngoscopy mean arterial pressure decreased and PaO2 increased with respect to the baseline values. During surgery all patients showed a good clinical relaxation. Thus, we believe that vecuronium is a good muscular relaxant agent, safe, and effective to be used in neurosurgery.


In the present study, experimental studies have been performed to compare the thermal performance of two geometrically identical box type solar (B-T-S) cookers. To carry out this aim, the thermal performance of BTS cooker in terms of figure of merits, namely, first figure of merit (F1) and second figure of merit (F2) are calculated for both cookers as specified by the Bureau of Indian Standards (BIS). At no-load condition (i.e., stagnation test), it is found that first figure of merit for both cookers that is cooker 1 and cooker 2 is around 0.12. This implies that both the cookers are identical in thermal performance. In addition to this, the effect of lugs height, reflector, number of pots, and load on B-T-S cooker performance have also been investigated. From the results and discussion, it is concluded that the use of lugs reduced the heat transfer rate between cooking pot and absorber plate. Further, it is found that the pot content temperature is enhanced by 25.5% and 23.4% by using mirror and aluminum reflector with cooker, respectively. However, it is observed that the performance parameters of B-T-S cooker in terms of F2 increases linearly with the increase of number of cooking pot (with correlation F2 = 0.0316n + 0.2238, where n is the number of pots) and load (correlation as F2 = 0.0451 m + 0.1844, where m is the mass of water in cooking pot) on the pot.


Objective: Bacteria- and fungus-binding mesh traps and inactivates bacteria and fungus, which makes it interesting, alternative, and wound filler for negative pressure wound therapy (NPWT). The aim of this study was to compare pathogen-binding mesh, black foam, and gauze in NPWT with regard to granulation tissue formation and ingrowth of wound bed tissue in the wound filler. Methods: Wounds on the backs of 8 pigs underwent 72 hours of NPWT using pathogen-binding mesh, foam, or gauze. Microdeformation of the wound bed and granulation tissue formation and the force required to remove the wound fillers was studied. Results: Pathogen-binding mesh produced more granulation tissue, leukocyte infiltration, and tissue disorganization in the wound bed than gauze, but less than foam. All 3 wound fillers caused microdeformation of the wound bed surface. Little force was required to remove pathogen-binding mesh and gauze, while considerable force was needed to remove foam. This is the result of tissue growth into the foam, but not into pathogen-binding mesh or gauze, as shown by examination of biopsy sections from the wound bed. Conclusions: This study shows that using pathogen-binding mesh as a wound filler for NPWT leads to a significant amount of granulation tissue in the wound bed, more than that with gauze, but eliminates the problems of ingrowth of the wound bed into the wound filler. Pathogen-binding mesh is thus an interesting wound filler in NPWT.


Wireless communication systems using multiple antennas at a transmitter, and many receivers, such as multiple-input multipleoutput (MIMO) broadcast systems, admit an application of a joint signal processing at the transmitter side. The algorithms that accomplish the task of joint signal processing that leads to enhanced performance of the MIMO broadcast systems are known as precoding algorithms. We consider a wireless MIMO broadcast system with white Gaussian noise, where the transmitter has multiple antennas, and each receiver is equipped with a single antenna. The knowledge of perfect channel state information (CSI) at the transmitter is assumed. The joint signal processing is admitted at the transmitter side, while the receivers are non-cooperative devices. The focus of this work is on the analysis of the MIMO system with finite number of transmit and receive antennas. In cellular systems, when the number of data streams is larger than the number of transmit antennas, and furthermore, the number of data streams exceeds a certain threshold number, the cellular systems become overloaded. In this work, an algorithm for vector precoding suitable for overloaded MIMO channels is proposed. It is shown that this algorithm can be used to increase the number of transmitted data streams significantly beyond the number of transmit antennas. The probability that this vector precoding algorithm, due to the channel singularity, fails to provide the data without crosstalk to the receiver is calculated analytically. This result is extended to the single-user MIMO channel in the presence of correlated Rayleigh fading, and more generally, arbitrary fading correlations. Non-overloaded MIMO system is considered in the rest of this work. The Hopfield neural network (HNN) is a powerful computational algorithm that belongs to the field of artificial neural networks (ANNs). A practical vector precoding algorithm using theHNNis derived, and analyzed by numerical simulations. The simulation results indicate that the HNN for vector precoding achieves the performance competitive to sphere encoder (SE) within wide system loads, where the system load is the ratio of the number of receive and transmit antennas. However, the degradation of the performance is exhibited in the MIMO broadcast system with the number of transmit antennas close to the number of receive antennas. Further improvement of the HNN for vector precoding algorithm is addressed by applying the Lenstra, Lenstra, Lov´asz lattice basis reduction (LLL-LR) algorithm. It is shown that the LLL-LR aided HNNfor vector precoding controls the energy penalty within the load range, where the sole HNN for vector precoding suffers from performance degradation. Computational complexity of the proposed algorithms is considered. The investigation of the number of iterations needed to be performed by the HNN algorithm until the convergence has been reached, indicates that small number of iterations is sufficient. The practical computational complexity of the HNN for vector precoding and LLL-LR aided HNN for vector precoding algorithms offers low-complexity alternatives to the SE within a wide range of loads. Characterization of the performance of vector precoding algorithms in terms of the spectral efficiency is the ultimate performance measure. We quantify the spectral efficiency of the minimum mean square error (MMSE) vector precoding algorithm by numerical simulations. Specifically, the performance metric is a normalized spectral efficiency (per transmit antenna). The discussion is restricted to the spectral efficiency of MMSE vector precoding with quadrature phase-shift keying (QPSK) signaling. The optimum system load that maximizes the spectral efficiency is obtained. The performance enhancement that MMSE vector precoding obtains in comparison to vector precoding with linear zero forcing (ZF) preprocessing, in the low to medium the energy per bit divided by the noise spectral density Eb N0 region, is quantified. We find that MMSE vector precoding does not significantly outperform its linear counterpart.


Purpose: This study examined the effects of exercise programs on the pain and quality of life in patients with knee osteoarthritis. Methods: Electronic bibliographic databases of KiSTi, KoreaMed, KISS and KERIS were searched to identify studies of randomized controlled trials and non-randomized controlled trials. As a result, 1213 publications identified and 16 studies met inclusion and exclusion criteria. All studies examined for quality assessment of studies using Cochrane's risk of bias. Results: The 16 studies were eligible for inclusion criteria, then the meta-analysis was conducted to examine effectiveness of exercise programs on pain and quality of life in patients with knee osteoarthritis. The meta- analysis based on the random effect model showed that the exercise program was beneficial in decreasing pain (effect size .69; 95% confidence interval 0.45~0.91). Also, the exercise programs have been shown to be effective in significantly improving the quality of life. However, it was not statistically significant due to severe deviations of studies (effect size 1.06; 95% confidence interval -0.34~2.46). Conclusion: Exercise programs had positive effects on pain relief and improvement of the quality of life in patients with knee osteoarthritis, although the quality of life was not statistically significant due to severe deviations of studies.


Predictions of future global warming suggest northward shifts of up to 800 km in the equilibrium distributions of plant species. Historical data estimating the maximum rate of tree distribution shifts (migration) suggest that most species will not keep pace with future rates of human-induced climatic change. Previous plant migrations have occurred at rates typically ranging from 15-50 km per century. A simulation model, which incorporates the effects of forest fragmentation and habitat loss, predicts maximum potential migration responses of trees may be only 1-10 km per century, or two orders of magnitude below that required to keep pace with predicted climatic warming. These predicted migration rates suggest that plants will fail to respond adequately to even modest climatic changes. Gauging the actual response of forest species to climatic change, and then appropriately managing forest resources poses several problems. First, we do not know the distribution limits of most forest species with the degree of precision to detect migration events on a 1-10 km scale. Second, many species may become vulnerable to extinction by their inability to migrate, leaving them geographically isolated from regions within their climatic tolerance. Third, while the distributions of species can be artificially expanded if climate does warm, this is not currently part of acceptable conservation management practice. Deciding whether or not to artificially enhance species ranges forces a choice between species preservation and historical community composition models for conservation. A pressing concern for forest management is to discover how climate change, anthropogenic habitat change, and doubled CO2 interact to alter forest species performance and regeneration within habitats they currently occupy. Range edges are the first place to look for key changes in these ecological responses.


Strongly Rayleigh (SR) measures are discrete probability distributions over the subsets of a ground set. They enjoy strong negative dependence properties, as a result of which they assign higher probability to subsets of diverse elements. We introduce in this paper Exponentiated Strongly Rayleigh (ESR) measures, which sharpen (or smoothen) the negative dependence property of SR measures via a single parameter (the exponent) that can be intuitively understood as an inverse temperature. We develop efficient MCMC procedures for approximate sampling from ESRs, and obtain explicit mixing time bounds for two concrete instances: exponentiated versions of Determinantal Point Processes and Dual Volume Sampling. We illustrate some of the potential of ESRs, by applying them to a few machine learning problems; empirical results confirm that beyond their theoretical appeal, ESR-based models hold significant promise for these tasks.


A taxonomic study was carried out on a novel strain, designated CK-I3-6(T), which was isolated from deep-sea sediment of the south-west Indian Ocean Ridge. Cells were Gram-reaction-negative, oxidase- and catalase-positive, rod-shaped and non-motile. Growth was observed at 4-38 °C and in 1-12 % (w/v) NaCl. Cells were able to degrade gelatin and oxidize thiosulfate but did not reduce nitrate. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain CK-I3-6(T) belonged to the genus Citreicella with a sequence similarity of 97.3 % to Citreicella thiooxidans CHLG 1(T), while similarities with other taxa were <95.7 %. DNA-DNA hybridization showed that strain CK-I3-6(T) and C. thiooxidans CHLG 1(T) showed a low DNA-DNA relatedness (48±3 %). The principal fatty acids were C(16 : 0) (7.8 %), C(18 : 1)ω7c (66.6 %), summed feature 3 (C(16 : 1)ω6c and/or C(16 : 1)ω7c; 6.3 %) and C(19 : 0)ω8c cyclo (10.0 %). The chromosomal DNA G+C content was 67.5 mol%. On the basis of the combined genotypic and phenotypic data, strain CK-I3-6(T) represents a novel species of the genus Citreicella, for which the name Citreicella marina sp. nov. is proposed. The type strain is CK-I3-6(T) ( = CCTCC AB 209064(T)  = LMG 25230(T)  = MCCC 1A03060(T)).


Purpose of reviewThis review evaluates recent findings on the mechanisms by which lipogenic enzymes are upregulated or activated in cancer cells, the implications of increased lipogenesis for cancer cell biology and the feasibility of exploiting this pathway and its regulators as targets for antineoplastic intervention. Recent findingsThe list of cancer types showing increased lipogenic enzyme expression keeps growing and further evidence is accumulating that growth factor signaling and particularly activation of the phosphatidylinositol 3′-kinase/protein kinase B pathway plays a role in this process. This signaling pathway stimulates lipogenic gene transcription through activation of the lipogenic transcription factor sterol regulatory element-binding protein-1 and directly activates lipogenic enzymes such as ATP-citrate lyase, linking the upregulation of lipogenesis in cancer cells to the well known tumor-associated increase in glycolysis. Steroid hormones, overexpression of the ubiquitin-specific protease-2a and mutations in breast cancer susceptibility gene 1 may further enhance lipid synthesis. While fatty acid synthase is further established as a target for antineoplastic intervention, recent findings show that interference with acetyl-CoA carboxylase-α, ATP citrate lyase or the AMP-activated protein kinase limits cancer cell proliferation and survival. SummaryThe same disturbances in signaling pathways responsible for oncogenic transformation may also contribute to the increased lipogenesis observed in tumor cells. Increased lipogenesis involves modulation of multiple lipogenic enzymes at both transcriptional and posttranscriptional level and is linked to other cancer-associated metabolic changes. Not only fatty acid synthase, but in fact all key enzymes involved in fatty acid synthesis as well as key metabolic regulators are potential targets for antineoplastic intervention.


This paper analyses the evolution of food retailing and describes how metaverses impact on it considering that retailers could be present in three different, but intertwined spaces. Our analysis deals with the major promotional issues, challenges and opportunities faced by traditional retailers, e-retailers and metaverse food retailers and the case of Second Life, a popular metaverse, is examined. A major finding is that retailers should apply a holistic approach when developing their promotional strategies aiming to have a presence in all three spaces. The authors suggest the pressing need for food policy development and stress the promotional and transactional potential that metaverses provide to other agri-food chain members including SMEs and manufacturers.


As the main coolant piping from the steam generator to the reactor pressure vessel, cold leg is an important part of the primary circuit. During a LOCA accident in the cold leg, the parameter sensitivity has a crucial influence for the containment response. PAREO program is used to analyze the sensitivity of the pressure response of HPR1000 containment. Quantitatively evaluated the influence of free volume, area of thermal components, spray flow rate and internal atmospheric temperature on the pressure and temperature of containment under the condition of LOCA. The results show that the area of thermal components is the most sensitive parameter to the pressure response process of containment. The research results could provide technical support for containment design, safety analysis and assessment.


The evolution of blockchain technology as a foundational and transformational technology helps solve critical societal problems. Blockchain technology enables sustainability-focused blockchain initiatives to achieve their social and public welfare objectives. Using a dataset of sustainability-focused blockchain initiatives, blockchain startups, and established businesses, the article evaluates the core transformational features of blockchain technology and its impact on humanity.


By combining scientific excellence with social involvement, M. S. Swaminathan has put himself in the tradition of the great agricultural researchers such as Von Liebich, Vavilov, De Vries, Haber and his friend and colleague Norman Borlaug that have defeated the Spectre of Malthus. His ability to use his knowledge and insights to find solutions for complex social problems made him one of the founding fathers of the Green Revolution. And one of the first that saw the drawbacks of the extensive use of water, fertilizer and pesticides that came along with it. He became a staunch advocate for the Evergreen Revolution towards an eco-friendly, resource-poor, sustainable agriculture that is based on science and technology and aims for nutrition security for all. Challenged with the perspective of feeding 9 or 10 billion people with sufficient and nutritious food and producing enough raw materials for the developing bio-based economy we have to keep on learning by doing research and combining its results with the experience of farmers and others. Yet there seems to be a lack of belief - at least in Europe - in human learning; a general distrust in science, which might lead to paralysis in agricultural development. Hence the biggest challenge is to bridge the gap between the sciences and society and to engage society in the development of science to meet the challenges of tomorrow.


A hybrid system is a dynamical system with both discrete and continuous state changes. For analysis purposes, it is often useful to abstract a system in a way that preserves the properties being analysed while hiding the details that are of no interest. We show that interesting classes of hybrid systems can be abstracted to purely discrete systems while preserving all properties that are definable in temporal logic. The classes that permit discrete abstractions fall into two categories. Either the continuous dynamics must be restricted, as is the case for timed and rectangular hybrid systems, or the discrete dynamics must be restricted, as is the case for o-minimal hybrid systems. In this paper, we survey and unify results from both areas.


Feasibility of detecting intravascular flow using a catheter based endovascular optical coherence tomography (OCT) system is demonstrated in a porcine carotid model in vivo. The effects of A-line density, radial distance, signal-to-noise ratio, non-uniform rotational distortion (NURD), phase stability of the swept wavelength laser and interferometer system on Doppler shift detection limit were investigated in stationary and flow phantoms. Techniques for NURD induced phase shift artifact removal were developed by tracking the catheter sheath. Detection of high flow velocity (~51 cm/s) present in the porcine carotid artery was obtained by phase unwrapping techniques and compared to numerical simulation, taking into consideration flow profile distortion by the eccentrically positioned imaging catheter. Using diluted blood in saline mixture as clearing agent, simultaneous Doppler OCT imaging of intravascular flow and structural OCT imaging of the carotid artery wall was feasible. To our knowledge, this is the first in vivo demonstration of Doppler imaging and absolute measurement of intravascular flow using a rotating fiber catheter in carotid artery.


Sixteen drug-free discharged remitted schizophrenics and twenty control subjects were tested on the Continuous Performance Test (CPT), a test of sustained attention. Following baseline testing, a distraction condition consisting of auditory and visual distractors was introduced. A third session without distractors represented a recovery period. Remitted schizophrenics failed to respond to critical stimuli (omission errors) during distractor period significantly more often than did controls. They more frequently responded to noncritical stimuli (commission errors). Response latency time for schizophrenics during recovery was prolonged. Poor premorbib schizophrenic subjects made significantly more commission errors than did good premorbib subjects. These results are interpreted as being compatible with a persisting attention deficit in clinically remitted schizophrenic patients.


ComK is a transcription factor required for the expression of competence genes in Bacillus subtilis. Binding to MecA targets ComK for degradation by the ClpCP protease. MecA therefore acts as an adapter protein recruiting a regulatory protein for proteolysis. However, when ComS is synthesized, ComK is released from binding by MecA and thereby protected from degradation. MecA binds to three protein partners during these processes: ComK, ClpC and ComS. Using limited proteolysis, we have defined N‐ and C‐terminal structural domains of MecA and evaluated the interactions of these domains with the protein partners of MecA. Using surface plasmon resonance, we have determined that the N‐terminal domain of MecA interacts with ComK and ComS and the C‐terminal domain with ClpC. MecA is shown to exist as a dimer with dimerization sites on both the N‐ and C‐terminal domains. The C‐terminal domain stimulates the ATPase activity of ClpC and is degraded by the ClpCP protease, while the N‐terminal domain is inactive in both of these assays. In vivo data were consistent with these findings, as comG–lacZ expression was decreased in a strain overproducing the N‐terminal domain, indicating reduced ComK activity. We propose a model in which binding of ClpC to the C‐terminal domain of MecA induces a conformational change enabling the N‐terminal domain to bind ComK with enhanced affinity. MecA is widespread among Gram‐positive organisms and may act generally as an adapter protein, targeting proteins for regulated degradation.


Two centuries ago, the German bacteriologist Robert Koch proposed three postulates to support a causal relationship between a specific microbe and an infectious disease. Similarly, three postulates are formulated here to help evaluate hypothetical proposals attempting to explain the pathogenesis of Alzheimer's disease (AD). The first postulate requires that the cause of AD precedes the cognitive decline and neurodegenerative pathology that characterize AD. This rule identifies a primary event from a neuropathological effect generated by the disease process. The second postulate stipulates that interventions aimed at the proposed causal event should prevent or reverse the cognitive and neurodegenerative pathology associated with AD prior to disease onset. This postulate emphasizes prevention or reversal of emerging neurocognitive pathology considerably before AD onset. If the first and second postulate requirements are met, the third postulate follows that interventions targeting the causal event should significantly lower the incidence of AD. For a causal hypothesis to be considered "likely" pathogenic to AD, support from all three postulates is a requisite. The pragmatic potential of the three postulates was applied to seven proposals using evidence-based meta-analysis mainly from randomized controlled trials. Proposals included the amyloid, cell cycle, cholinergic, inflammatory, oxidative stress, tau, and vascular hypotheses. Clinical evidence derived from each proposal formed the basis for an inferential conclusion based on the level of confidence provided by the trial data. The three postulates may challenge or help validate a proposed cause-effect relationship to AD and serve as a useful model for designing more intelligent therapeutic interventions aimed at preventing AD.