Supervised learning requires the specification of a loss function to minimise. While the theory of admissible losses from both a computational and statistical perspective is well-developed, these offer a panoply of different choices. In practice, this choice is typically made in an \emph{ad hoc} manner. In hopes of making this procedure more principled, the problem of \emph{learning the loss function} for a downstream task (e.g., classification) has garnered recent interest. However, works in this area have been generally empirical in nature.
In this paper, we revisit the {\sc SLIsotron} algorithm of Kakade et al. (2011) through a novel lens, derive a generalisation based on Bregman divergences, and show how it provides a principled procedure for learning the loss. In detail, we cast {\sc SLIsotron} as learning a loss from a family of composite square losses. By interpreting this through the lens of \emph{proper losses}, we derive a generalisation of {\sc SLIsotron} based on Bregman divergences. The resulting {\sc BregmanTron} algorithm jointly learns the loss along with the classifier. It comes equipped with a simple guarantee of convergence for the loss it learns, and its set of possible outputs comes with a guarantee of agnostic approximability of Bayes rule. Experiments indicate that the {\sc BregmanTron} substantially outperforms the {\sc SLIsotron}, and that the loss it learns can be minimized by other algorithms for different tasks, thereby opening the interesting problem of \textit{loss transfer} between domains.


Nutrition and health claims can help consumers identify foods that are healthier. The pan-European CLYMBOL study found that 21% of prepacked foods carry nutrition claims while health claims were found on 11% of foods, mostly in the form of general (non-specific) health claims. However, foods carrying claims had only marginally better nutritional quality than those that did not. Assessment of food labelling information was also conducted, revealing major issues related to the use of nutrition and health claims. The development of food labels is an important step in delivery of prepacked foods that needs more attention from food manufacturers. CLYMBOL recommended that food business operators should ensure that nutrition and health claims are not used on foods with unfavourable nutrition composition. Good practice was shown by some producers through the introduction of internal nutrition profiles to limit use of claims to healthier foods. Additionally, statements on non-specific benefits of a product for overall good health or health-related well-being need to be used with care. Such statements can be helpful for consumers, as they convey more consumer-friendly messages than many authorised claims, but these can also be misunderstood, misleading consumers about potential health benefits.


This guide provides a set of resources, available through the CCNY's Library for beginning research in computer science and/or computer engineering. This list is not exhaustive or comprehensive. Visit our home page for additional resources.


Background: Circulating 25 hydroxyvitamin D (25 (OH)D), an accurate measure of vitamin D status, is markedly reduced in rachitic infants. Aside from the known relationship between vitamin D and bone, vitamin D has also been implicated in cardiovascular homeostasis, immune function and inflammation. Furthermore, a mass of evidence is accumulating that vitamin D deficiency could lead to cardiovascular complications and imbalance of cytokines profile. Our objective was to study the relationship between vitamin D status (as determined by serum25(OH) D concentrations) and inflammatory markers and left ventricular function in rachitic infants, also to evaluate the effect of vitamin D supplementation on the above parameters. Subjects and methods: This study included two groups; vitamin D deficiency rickets (VDDR) group (25 infants) and an age matched control group (15 infants). After subsiding of the acute illness, the rachitic infants received vitamin D supplementation for 6 months. Blood samples were collected in the morning before the start of treatment and analyzed for serum 25(OH)D, intact parathyroid hormone (iPTH), Alkaline phosphatase (ALP), calcium (Ca), Phosphorus (Ph) and inflammatory markers [interleukin-6 (IL-6), and C-reactive protein (CRP)]. Electrocardiogram (ECG) and echocardiography measuring left ventricular functions were done. The biochemical variables, ECG and echocardiography were assessed at baseline and after 6 months of vitamin D supplementation. Results: VDDR group had significant lower 25(OH)D, Ca, Ph and significant higher iPTH, ALP, IL-6 and CRP compared to the age matched control group at baseline. Echocardiographic finding revealed significant increase in LVEDD and LVESD and significant decrease in EF% and FS% in VDDR group compared to the age matched control group at the study entry. Also, ECG finding showed abnormality in some patients at baseline. The biochemical, echocardiographic and ECG variables improved significantly after 6 months of vitamin D supplementation and reached to those levels found in the age matched control group. Finally, we found negative correlations between 25(OH)D level and IL-6, CRP, LVEDD and LVESD. Also, positive correlations were found between 25 (OH)D and EF% and FS%. These correlations were observed at baseline and after 6 months of vitamin D treatment. Conclusion: VDDR is associated with increased inflammatory markers and impairment of left ventricular functions in rachitic infants. Vitamin D supplementation ameliorated these effects. Also, results gleaned from this investigation support the possible contributing role of the elevated inflammatory markers in the pathophysiology of left ventricular impairment in vitamin D deficiency rachitic infants. More studies are needed to fully characterize the relationship between Vitamin D induced inflammation and cardiac function in rachitic infants. Bull. Egypt. Soc. Physiol. Sci. 32 (2) 2012 Abdelhaffez & Metwalley 158


The 13CO (J=1-0) map of the molecular cloud Sgr B2 reveals that the mass center of the molecular cloud nucleus does not coincide with that of compact HII regions which are likely to be the outcome of a shock on the cloud.We find evidence of cloud contraction probably resulting from cloud-cloud collision at subsonic speed.


Acoustic telemetry techniques are very useful tools to monitor in detail the swimming behavior and spatial use of fish in artificial rearing environments at individual and group levels. We evaluated the feasibility of using passive acoustic telemetry to monitor fish welfare in sea-cage aquaculture at an industrial scale, characterizing for the first time the diel swimming and distribution patterns of gilthead seabream (Sparus aurata) at fine-scale. Ten fish were implanted with acoustic tags equipped with pressure and acceleration sensors, and monitored in a commercial-size sea-cage for a period of 1 month. Overall, fish exhibited clear differences in day vs. night patterns both on swimming activity and vertical distribution throughout the experiment. Space use increased at night after the implementation of structural environmental enrichment in the sea-cage. Acoustic telemetry may represent an advancement to monitor fish farming procedures and conditions, helping to promote fish welfare and product quality.


Pipelines are used widely to convey fluids and gases in the petrochemical, water, and energy sectors. Vibration, noise and fatigue failure of pipelines are serious problems in many engineering situations, especially in ship and ocean engineering areas. In this paper, the acoustic propagation and attenuation characteristics of axisymmetrical eigenmodes in a cylindrical, elastic, fluid-filled pipe are investigated analytically. Pipe equations for n=0 axisymmetrical wave motion are derived, and analytical expressions of wavenumber are obtained for s=1 and s=2 wave, which correspond to a fluid dominated wave and an axial shell wave, respectively. The numerical results for wavenumber of pipe and fluid are obtained and discussed. It shows that the frequency dependent phase velocity of this mode depend strongly upon the shell thickness/radius ratio and the density of the contained fluid. It seems that this analysis method is simple and effective.


Fever represents the major surrogate of infection in neutropenic cancer patients. A number of neutropenic fever syndromes have been recognized, the causes and significance of which will vary depending upon the clinical context. First neutropenic fever syndromes are typically of bacterial origin, the character of which may be influenced by whether antibacterial chemoprophylaxis has been administered. Persistent neutropenic fevers are documented during the empirical systemic antibacterial therapy for the first neutropenic fever, the cause of which is likely outside the spectrum of activity of the initial therapy. Recrudescent neutropenic fevers, defined by the appearance of a new fever after defervescence of the first fever, are often a function of invasive fungal infection or gram-positive infections outside the spectrum of the initial empirical antibacterial regimen. The myeloid reconstitution syndrome occurs in parallel with neutrophil recovery from aplasia and may not necessarily represent new infection. Recognition of these patterns can help the clinician make better clinical judgments and management plans.


Some volcanoes erupt explosively, with magma rapidly expelled as a hot jet of gas. The processes by which the magma is converted into the hot jet are still poorly understood. As discussed in the Perspective by Vergniolle, recent research reported by Morrissey and Chouet in the same issue (p. 1290) may shed light on these violent events. Data obtained with a network of microbarographs, or pressure sensors, can be used to estimate the pressure of the exiting gas jet.


value of photic radiations) are well known, one wonders why no epidemiological survey of seasonal affective disorder has been undertaken. Presumably congenitally blind people could provide controls worth exploring, other psychological drawbacks notwithstanding. Is the condition more pronounced among the Eskimos, who probably use less artificial light than Swedes? When travelling through Peru I was struck by the paucity of artificial illumination in rural areas. Is anything known about psychiatric conditions there or is life too hard for seasonal affective disorder to flourish? What happens near the equator, where seasonal variations ought to be minimal? Relevant expert epidemiological studies might provide a short cut to meaningful results, which might elude an apparently more direct approach.


We explore the tradeoff between player autonomy and designer intent by simulating a system of autonomous museum tour guides. Visitors may have different art preferences or may wish to visit different exhibits on multiple visits. Often, these desires conflict. For example, visitors may wish to see the museum's most popular work, but that could cause congestion, ruining the experience. Thus, our task is to build a set of guides that can satisfy their visitors' goals while also providing quality experiences for all. We present the results of a case study indicating that there is a space in the design spectrum between fully author-controlled narrative and complete player autonomy that reduces the frequency of bad experiences while allowing visitors to realize their own goals.


Oral fluid is often called the 'mirror of the body'. The noninvasive nature of salivary testing has made it an attractive and effective alternative to blood and urine. Use of saliva has become more extensive in recent years, particularly in relation to estimation of systemic levels of lipid-soluble drugs and hormones. Furthermore, saliva may provide a cost-effective approach for the screening of large populations. Gland-specific saliva can be used for diagnosis of pathology specific to one of the major salivary glands. Saliva as a whole, however, is most frequently used for diagnosis of systemic diseases, since it is readily collected and contains serum constituents. As a diagnostic fluid, saliva offers distinctive advantages over serum because individuals with modest training can collect it non-invasively. This review presents the translational value of saliva as a credible clinical diagnostic fluid and the scientific rationale for such use.


A trial involving a 2x2 factorial arrangement of treatments was conducted to evaluate two corn silage hybrids (Agromen, AGN35-A42) and (Bayer, A3663) and concentrate levels (25 and 50%) on animal performance. Twenty-four Holstein x Zebu crossbred steers, averaging 335±30kg of BW, were distributed in six randomized blocks to evaluate intake, digestibility, and performance. Treatments consisted of 75% corn silage A + 25% concentrate, 50% corn silage A + 50% concentrate, 75% corn silage B + 25% concentrate, and 50% corn silage B + 50% concentrate (dry matter basis); formulated to be isonitrogenous (13% crude protein, dry matter basis). There were no differences in the daily intakes of dry matter (DM), organic matter (OM), and crude protein. Additionally, there was a concentrate effect on non-fiber carbohydrates and total digestible nutrients intakes, and on total apparent digestibility of DM and OM, with higher intakes for steers fed diets with 50% of concentrate. However, average daily gain (ADG) was not influenced by treatments. The utilization of both corn silage hybrids in association with 25% of concentrate is a good option to feed crossbred steers with ADG close to 1.0kg in order to reduce diet cost.


This article provides an insight into the role of a full-time supervisor of midwives (SoM) at Barking, Havering and Redbridge University Hospitals NHS Trust (BHRUT). The role was the first of its kind in London and was introduced in response to concerns raised by a Care Quality Commission review (CQC) of maternity services in October 2011. The report made 79 recommendations to the Trust, 15 of which related to maternity services. It was evident many SoMs were overwhelmed with day-to-day difficulties, working in their own time to ensure the statutory function of supervision was being provided to all midwives. Day-to-day supervision needed to be improved for junior inexperienced midwives needing support, and the ratio of SoMs to midwives needed to reflect those recommended in Nursing and Midwifery Council (NMC) 2012a) guidance. An explanation of how the role evolved is given, highlighting the challenges and benefits encountered. The article concludes by evaluating the role to date.


This article examines three fundamental questions with respect to the place of e-government in graduate education for careers in public service. First, where does e-government fit in the curriculum of graduate programs in public policy and administration? Second, might we expect the answer to this question to vary depending on the institutional home and type of public affairs degree? Third, should we expect programs to offer a required course on e-government or should we aim to integrate material on e-government throughout the curriculum? These questions are approached through standards developed for public affairs education in the United States, but they are examined in the context of international variations in governance, technology and education. The article first traces the development of e-government across the globe, summarizing important issues and consideration that government must answer as they pursue e-government initiatives. It then reviews standards that have been developed for public affairs education in the U.S. and turns to the question of how to incorporate e-government in the curriculum. E-government involves much more than technological and information management questions. Thus, it has implications for the entire public affairs curriculum. It is unlikely that a single course can successfully covers technical, managerial, and policy dimensions of e-government. For most programs, it will be more productive to explore e-government across a range of courses in the existing curriculum. The approach that is taken is likely to be affected by institutional settings, resources, and faculty competencies. It is also likely to be shaped by the broader social, economic, and political environments in which programs operate. Although the stage of e-government development in the country is likely to make a difference, we can also hope that our training will also shape e-government's development.


A 66-year-old man with pancreatic cancer developed an anastomotic leakage of the pancreaticogastrostomy 15 days after pylorus-preserving pancreaticoduodenectomy. An easy-flow drain was identified endoscopically in the extraluminal cavity. Two-sided sponge (TSS) treatment was initiated [1]. A gastric tube was attached to the outer end of the drain with adhesive tape (Opsite Flexfix; Smith & Nephew Medical, Hull, UK). The drain was then grasped inside the cavity with a forceps (foreign-body removing forceps; MTW Endoskopie Manufaktur, Wesel, Germany) (▶Fig. 1, ▶Video1). The drain was orally removed, with the gastric tube still attached to its end. The TSS (Braun, Melsungen, Germany) (▶Fig. 2) was connected to the gastric tube by adhesive tape, and was drawn into the cavity by pulling the abdominal end of the gastric tube. The oral end of the TSS tube was nasally diverted (▶Video1). Both ends of the TSS tube were connected to a vacuum pump (−30mmHg). When the TSS was changed at day 5, a clean cavity was seen (▶Fig. 3, ▶Video1). At day 9, sponge-induced granulation tissue was seen (▶Video1). A rubber drain was introduced (▶Fig. 4) to promote the formation of granulation tissue and thus definitive healing. At day


This study was aimed at getting to know the relationships built among patients, family caregivers and the health care team, during home care,from the perspective of the family caregiver It is a qualitative study with 11 family caregivers of terminal patients, registered on a home care service of a university hospital in the South of Brazil. Data collection was carried out through narrative interviews that were recorded transcribed and analyzed through content analysis. Three categories were built from data analysis: relationships among the family caregiver, the patient and the health care team; awareness of the patient's terminal condition. the caregiver's perspective; and situation in which patients are unaware of their terminal condition. They approach how the home care relationships are established among the caregivers, such as health care professionals and family caregivers, and the people who are taken care of such as the patients, highlighting the importance of communication in such care related context.


A guide to North Carolina resources & services in the NC Government & Heritage Library and at institutions around NC.


A 52-year-old male developed bilateral subepithelial amorphous corneal deposits as well as diffuse noniridescent anterior stromal haze of unknown etiology. The deposits increased in density and a penetrating keratoplasty was performed in one eye when vision became sufficiently compromised. Pathological evaluation of the tissue included light and electron microscopy and immunohistochemical studies. The deposits were identified as monoclonal IgG kappa immunoglobulins and a systemic workup confirmed the diagnosis of a previously unsuspected multiple myeloma. The clinical course was characterized by the noncrystalline nature of the deposits, recurrence of the myeloma protein within the graft, and the poor response of the cornea to systemic therapy. In addition, profound ocular morbidity occurred, with a final visual acuity of 20/200 OD and 20/400 OS.


In recent years, with the widespread of Internet and digitized processing of multi-script documents worldwide, script identification techniques have become more important in the pattern recognition field. Script identification concerns methods for identifying different scripts in multi-lingual, multi-script documents. This paper presents a comprehensive overview on research activities in the field and focuses on the most valuable results obtained so far. The most vital processes in script identification are addressed in detail: identification and discriminating methods, features extraction (local and global), and classification. Different kinds of approaches have been developed and promising results have been achieved. This paper reports SoA performance results. This paper reports methods concerning handwritten, printed, and hybrid document processing. More research is necessary to meet the performance levels essential for everyday applications.


Organizations with social missions, such as nonprofits and social enterprises, are under growing pressure to demonstrate their impacts on pressing societal problems such as global poverty. This article draws on several cases to build a performance assessment framework premised on an organization's operational mission, scale, and scope. Not all organizations should measure their long-term impact, defined as lasting changes in the lives of people and their societies. Rather, some organizations would be better off measuring shorter-term outputs or individual outcomes. Funders such as foundations and impact investors are better positioned to measure systemic impacts. (Keywords: Performance Measurement, Scale, Scope, Mission, Nonprofit, Social Enterprise)


The quest for higher performance within a certain power budget in the fields of embedded computing demands unconventional architectural approaches. To this end, in this paper we present synZEN (sZ): a (micro-)architecture that combines features of very long instruction word (VLIW) and transport triggered architectures (TTAs) to cover the needs of different applications. SynZEN features a distributed register file (RF) (i.e., each functional unit (FU) has its own RF) and a wide memory connection to exploit spatial data locality. FPGA synthesis results demonstrate that due to the distributed RF the sZ design can be implemented in less area (in terms of FPGA slices) than existing TTA and VLIW designs. Furthermore, using two micro-benchmarks we show that because of the wide memory connection, sZ outperforms both the TTA as well as the VLIW design.


This paper attempts to develop a comprehensive model for the problem of internal vs. external conjunction (Halliday & Hasan 1976). It is first argued that the distinction between internal and external conjunction is not merely a matter of semantics, but that the two types are semiotically significant categories. By postulating that internal and external conjunction are cryptotypically anchored in the speaker-encoding vs. content-related grammar of their main clause, it can be explained why and how syntactic criteria like clefting or nominalization 'react' to the semantic distinction between the two types of conjunction. Secondly, it is argued that the internal category should be subdivided into two grammatically distinct types of conjunction, which are related to the modal and the speech functional grammar of their main clause. Finally, this analysis is used to propose a sharper delineation of the modal and the speech functional subtypes of the internal category.


Abstract Facial expressions play a fundamental role in interpersonal communication and interaction; consequently, facial palsy has profound effects on the quality of life of patients. Reanimation of lower lip depressors is rarely addressed during facial reanimation but is as important as treating the eye sphincter and the lip levators. Depressors of lower lip are vital for full denture smile and the expression of facial emotions. Static and dynamic techniques are used to reanimate the lower lip depressors. Static techniques provide stationary results either by weakening the contralateral normal side to achieve symmetry using botulinum toxin injection, depressor labi inferioris myectomy and marginal mandibular nerve neurectomy, or by creating static slings and tightening procedures on the affected side. Dynamic techniques provide functional results by reanimating the affected depressor complex using nerve transfers, muscle transfers, and direct muscle neurotization. The purpose of this article is to present an overview of the literature on the applications of these techniques in lower lip reanimation. Furthermore, preoperative evaluation and indications are also discussed.


Tuberous sclerosis is an autosomal dominant multisystem disorder characterised by the development of benign tumours in many organs, including the brain, skin, kidneys and heart, seizures and intellectual disability. The condition results from mutations in either of two genes, TSC1 (encoding TSC1) or TSC2 (encoding TSC2). Loss of functional TSC1 or TSC2 leads to activation of mTORCl (mammalian target of rapamycin complex 1), a key regulator of multiple cellular processes including cell growth and division. Lymphangioleiomyomatosis (LAM) is a lung disorder which can lead to respiratory failure and is characterised by the proliferation of abnormal 'LAM' cells LAM occurs in patients with tuberous sclerosis and can also occur as a sporadic disorder due to acquired mutations in TSC2. Renal angiomyolipomas are benign tumours which affects80% of patients with tuberous sclerosis and 40% of patients with sporadic LAM. Sirolimus is an inhibitor of mTORCl and is used in clinical practice as an immunosuppressant. Preclinical studies suggest that TSC1 or TSC2 deficiency renders cells sensitive to mTOR inhibition. This thesis describes a phase 2 trial to assess the safety and efficacy of 2 years of treatment with sirolimus for renal angiomyolipomas in patients with tuberous sclerosis or LAM. Response of angiomyolipoma was the primary efficacy end point. Effects of sirolimus on lung function and neurocognitive function are also reported. Our data show an angiomyolipoma response rate, by RECIST criteria, of 50% in the intention to treat population. There was little change in lung function. Recall but not recognition memory tended to improve. Adverse events were common and consistent with the known toxicities of sirolimus. Our findings suggest that mTOR inhibition is a potential therapeutic strategy in the treatment of tuberous sclerosis and lymphangioleiomyomatosis.


SUMMARY
We report a software scheme for automated diagnosis of liquid chromatography tandem mass spectrometry (LC-MS/MS) system performance. The proposed software scheme provides a robust framework for establishing automated diagnosis of LC-MS/MS system performance for a variety of instruments and experiments. This schematic consists of four main software components: (i) data conversion, (ii) peptide identification, (iii) LC retention time analysis and (iv) system performance evaluation. The implementation of a standard approach for assessing LC-MS/MS system performance enables researchers to apply reliable metrics to assess their workflows performance over different batch experiments. Furthermore, the results from system diagnosis can provide feedback to the workflow to stop batch analysis if system performance falls below prescribed thresholds. A basic implementation of the approach based on the MassMatrix database search and LC retention time analysis programs is presented.

AVAILABILITY
An open source implementation of the LC-MS/MS system diagnosis software based on the MassMatrix database search program is freely available to non-commercial users and can be downloaded at www.massmatrix.net.


Abstract. We analysed results of three intensive aircraft campaigns above Siberia (April and September 2006, August 2007) with a total of ~70 h of continuous CO2, CO and O3 measurements. The flight route consists of consecutive ascents and descents between Novosibirsk (55° N, 82° E) and Yakutsk (62° N, 129° E). We performed retroplume calculations with the Lagrangian particle dispersion model FLEXPART for many short segments along the flight tracks. To reduce the extremely rich information on source regions provided by the model calculation into a small number of distinct cases, we performed a statistical clustering – to our knowledge for the first time – into potential source regions of the footprint emission sensitivities obtained from the model calculations. This technique not only worked well to separate source region influences but also resulted in clearly distinct tracer concentrations for the various clusters obtained. High CO and O3 concentrations were found associated with agricultural fire plumes originating from Kazakhstan in September 2006. A statistical analysis indicates that summer uptake of CO2 is largely explained (~50% of variance) by air mass exposure to uptake by Siberian and sub-arctic ecosystems. This resulted in an average 5 to 10 ppm difference with overlaying air masses. Stratosphere-troposphere exchange is found to strongly influence the observed O3 mixing ratios in spring, but not in summer. European emissions contributed to high O3 concentrations above Siberia in April 2006 and August 2007, while emissions from North Eastern China also contributed to higher O3 mixing ratios in summer, but tend to lower mixing ratios in spring, when the airmass aerosol burden is important. In the lower troposphere, large-scale deposition processes in the boreal and sub-arctic boundary layer is a large O3 sink, resulting in a ~20 ppb difference with overlaying air masses. Lagrangian footprint clustering is very promising and could also be advantageously applied to the interpretation of ground based measurements including calculation of tracers' sources and sinks.


In order to reduce the passivity of students and enhance their learning experience in large lectures, we developed a browser-based tool called Classroom Interacter to promote classroom interaction. It allows students to use their own mobile devices to participate in the learning process. The main features of Classroom Interacter include live voting, status setting and question sending. The evaluation results showed that, students were satisfied with the usability and felt it was helpful for their study. Although distraction was reported by some students, the system received very positive evaluations. Most students showed their willingness to use Classroom Interacter in the future.


Modern Real Time Operating Systems require reducing computational costs even though the microprocessors become more powerful each day. It is usual that Real Time Operating Systems for embedded systems have advance features to administrate the resources of the applications that they support. In order to guarantee either the schedulability of the system or the schedulability of a new task in a dynamic Real Time System, it is necessary to know the Worst Case Response Time of the Real Time tasks during runtime. In this paper a reduced computational cost algorithm is proposed to determine the Worst Case Response Time of Real Time tasks.


During the last century, airbases were attacked at least 26 times in an effort to destroy the enemy at its base. Attacks on military airbases impose prohibitive losses to critical infrastructure, which in turn impacts the maintenance of air power projection. The primary enemy threat facing critical infrastructure today is the use of ballistic and landattack cruise missiles to disrupt an airbase's ability to launch and recover aircraft. Over the last decade, ballistic and cruise missile technology has grown to allow the world's most powerful countries to achieve a nascent threat to forward operating bases used in theater security campaigns worldwide. Planners can reduce the impact of ballistic and cruise missile attacks on aircraft projection platforms by incorporating a number of resiliency measures, including dispersal of critical infrastructure assets, such as aircraft fuel containment and conveyance equipment. The integration of resiliency measures increases construction costs; therefore, planners need to identify an optimum balance between maximizing airbase resiliency and minimizing site costs. This research presents an airbase resiliency assessment capable of quantifying facility dispersal and risk tolerance levels in an environment threatened by missile attack. Model performance was evaluated using a case study from Osan AB, Republic of Korea. The model's distinctive capabilities are expected to support planners in the critical task of analyzing and selecting the design strategy that maximizes airbase resiliency against the threat of ballistic and cruise missile attack.


Small Hospitals: Efficiency and Economy SIR,-" Hospital Survey: The Hospital Services of London and the Surrounding Area," that formidable-looking Blue Book, has by now probably been seen by all those interested in hospital work, whether layman or doctor, and it will be agreed by all that Drs. Gray and Topping have carried out their task in an impressively comprehensive manner and with an efficiency which could not be excelled. The statistical tables which form the largest portion of the book are of the greatest value to hospital organizers, and to my knowledge are in constant consultative use in most hospitals. We must all, therefore, be appreciatively grateful for the tremendous labour which the authors have put into such a Herculean work. But, having paid tribute to " Hospital Survey," we should not let our appreciation blind us to the fact that, like many other such reports, it was produced under certain conditions and auspices which have an influence upon its recommendations. I refe-r to the knowledge that the survey was undertaken at the instigation of the Minister of Health in 1941 and that there must of necessity have been terms of reference. What these terms were is not quite certain; but, whether definitely stated or merely implied, it is clear from reading the report that they involved the idea of discovery whether -the hospital services could be more efficiently and economically (not only in the financial sense) run. If this was indeed the real state of affairs it must be constantly borne in mind when considering the report that it had a restricted aim in view, and all its recommendations should be seen in the light of those restrictions. In other words, the report now becomes the opinion of two well-informed minds upon the possible change which would make for greater efficiency and econiomy of working. Such a viewpoint immediately changes one's reactions to the Blue Book, for when I regard the report as a complete survey of hospital activities I cannot escape the conviction that it is a completely soulless document; but if I think of it as an essay upon the possible changes which might lead to greater efficiency and economy then the book stands in a different category, for I am now at liberty to ask what efficiency in medical work means, and whether it is to be the be-all and end-all of medical ambition. Efficiency is difficult to define; who knows what efficiency in its medical application is? Medicine changes so rapidly that what is worshipped as efficiency to-day becomes a clay-footed idol to-morrow. When our dramatic critics say that Miss A.'s acting was efficient, what do we think? Were Turner's paintings, Shakespeare's plays, efficient? Surely we have to think of more in medicine than efficiency. Supposing the Home Secretary asked for a "Family Survey " it would be possible for an assiduous worker to produce a report the logic of which was beyond challenge, but it would of necessity have to contain such statements as: "We found that the one-child famiWy is inefficient and uneconomic, and so we .suggest that all children from such families be transferred to the larger families of four or more children." Irrefutable logic, once we accept that efficiency and economy of effort are the final aims. This brings me to the main point of this letter, for I notice that it is proposed to turn many of the small hospitals into mere annexes of the larger, for the reception of convalescent patients and the like. The basis for this suggestion is that the small hospital is inefficient and uneconomic. I cannot agree for two reasons: in the first place, as I have tried to explain. I do not think that in matters of medical treatment we should raise efficiency to a god-like status; in the second place I do not believe that most of these small hosoitals are inefficient when judged by the only criterion that matters-namely, resuilts. It is my privilege to work in both classes of hospital, from over 1,000 beds on the one hand to 50 on the other, and I find that my results are as good in the one as in the other-this for major surgery. I am, of course, not ignorant of the fact that there are certain very highly specialized types of treatment which the small hospital is. not equipped to undertake. Cases requiring such treatment, however, make up a very small percentage of the whole and can be dealt with by affiliation with a large insticution. The intangible factors connected with the small hospitallocal pride and faith in the, institution and so on-cannot unfortunately be estimated by statistical tables suitable for reprcduction in " Hospital Survey," but they are in my opinion -more important to the well-being and happiness of the patient than a lot of efficiency, which in any case is not lacking. What the legal implications of the recommended changes are I have no means of knowing, but it is certain that in many instances the money for starting and running such small hospitals has been given specifically because they are what they are. I suppose an omnipotent Parliament can change any law, good or bad, so that this difficulty may not require consideration. Since writing the above I have had an opportunity of reading the report of the King's Fund upon the same subject, and I note with pleasure that, with certain safeguards, its recommendations are favourable to the retention of the small and cottage hospitals, and that the authors display a keen appreciation of the human as well as the humane side of hospital work. -1 am, etc.,


Summary The importance of regulatory T lymphocytes (Tregs) in the control of autoimmunity is now well established in a variety of experimental animal models. In addition, there are numerous studies suggesting that Treg deficits may be an underlying cause of human autoimmune diseases. The emergence of Tregs as an essential component of immune homeostasis provides a potential therapeutic opportunity for active immune regulation and long‐term tolerance induction. In this article, we summarize the core basic science and animal model studies of Tregs, review the status of multiple biologic and small molecule chemical compounds to promote Treg development in vivo, and discuss recent advances for the identification and expansion of polyclonal and antigen‐specific Tregs for adoptive immunotherapy. In summary, the review provides an in‐depth analysis and highlights the challenges and opportunities for immune intervention with Treg‐based therapeutics.


Patterns emerge in various growing biological organisms, like conifer embryos, often from an homogeneous preceding state. The embryo tip, initially hemispherical shaped gradually flattens as cotyledons arranged in a roughly regular pattern emerge. A common way to model these patterns is through reaction-diffusion systems of partial differential equations. This thesis relays results obtained studying such systems and provides various new results about pattern formation on curved surfaces via diffusion driven bifurcations. We first describe situations where, for certain critical values of domain or differential equation parameters, the unpatterned solution is unstable to two different linear normal modes. We use centre manifold and normal form reductions to analyze the existence and stability of pure and mixed modes of nonlinear patterned solutions of the reactiondiffusion system, for parameters near two cases of critical values. In one case, the system reduces to a well known example of mode interaction. In the other case, the mode interaction is new, due to very small quadratic terms in the normal form. We then perform a reduction of a nonautonomous Brusselator reaction-diffusion system of partial differential equations on a spherical cap with time dependent curvature using an asymptotic series expansion on the centre manifold reduction. Parameter values are chosen such that the change in curvature would cross critical values which would change the stability of the patternless solution in the constant domain case. The nonisotropic nature of the domain evolution insert a small patterned component to the previously patternless state, which we call the 'quasi-patternless solution'. The evolving domain functions and quasi-patternless solutions are derived as well as a method to obtain this nonautonomous normal form. The obtained reduction solutions are then compared to numerical solutions. Finally we provide an adaptation of the closet point method to evolving domains. We perform several convergence analysis experiments of the heat equation on test surfaces and obtain quadratic convergence. Then, a few reaction diffusion simulations are shown on evolving surfaces, some featuring non-isotropic evolution. The previously shown application of the Brusselator system on an evolving spherical cap are compared to a centre manifold reduction and also show quadratic convergence.


Expansions of short repeats—those with units of ≤12 bp—account for as many as 40 diseases [1]–[4]. About half of these disorders arise from expanded tracts of CAG/CTG triplets, many encoding polyglutamine. Since the discovery of the first polyglutamine-encoding CAG repeat disorder in 1991 [5], the predominant hypothesis has been that pathogenesis of the CAG category is a consequence of a toxic gain-of-function of excessively long strands of polyglutamine. Polyglutamine toxicity has been most systematically explored in Huntington's disease (HD), with evidence that it influences multiple processes, including transcriptional regulation, mitochondrial energy production, and calcium regulation. This proteocentric view is undergoing considerable revision, as mounting evidence suggests toxic roles for mutant transcripts in HD [6] (Figure 1). The initial clues regarding CNG transcript toxicity emerged from studies of myotonic dystrophy type 1 (DM1). DM1 is caused by an expanded CTG repeat located in the 3′ end of the DMPK gene. Transcripts with long CUG repeats dysregulate the splicing factors MBNL1 and CUGBP1, leading to aberrant splicing of numerous downstream transcripts; dysfunction of these proteins directly correlates with various features of the disease phenotype. Subsequently, multiple lines of evidence have emerged that RNA toxicity contributes to the pathogenesis of other CAG/CTG disorders. Structurally, RNA with sufficiently long stretches of CUG or CAG triplets can form hairpin structures likely to influence the affinity of RNA binding proteins [7]. At least partly as a consequence of these structures and changes in protein binding, transcripts with either type of repeat may aggregate into discrete foci that include MBNL1 [8], [9]. In HD, RNA foci and misregulation of splicing have been detected in peripheral HD tissue [9]. The potential toxicity of transcripts containing long CAG tracts has been demonstrated in fly, worm, and mouse systems [10]–[14]. HDL2, a disorder clinically and pathologically similar to HD, involves CUG transcript toxicity mediated by dysregulation of MBNL1 [15], [16]. A second potential mechanism of CAG/CTG toxicity emerged from evidence that bidirectional transcription through the HTT repeat region [17] is a source of Dicer-generated CAG/CUG repeat siRNAs capable of targeting cellular transcripts containing complementary repeats [18].

Figure 1

RNA contribution to HD pathogenesis.

In this issue of PLoS Genetics, Banez-Coronel and colleagues [19] provide further evidence for the involvement of HTT RNA and the RNAi pathway in HD pathogenesis. The authors demonstrate that overexpression of translatable and non-translatable HTT exon 1 constructs with expanded CAG repeats leads to Dicer-dependent production of short CAG repeat RNAs (sCAGs) with cytotoxic properties. Cytotoxic effects are triggered by expanded CAG repeats (which can form RNA hairpins), but not by expanded CAA repeats (which, like CAG, encode glutamine, but cannot form hairpins), consistent with recent findings in a fly model [11]. sCAG species were detected in Ago-2 complexes, supporting association with RNAi pathways. Antisense inhibitors of the sCAG species reverse cytotoxicity, and sCAGs were detected in R6/2 HD transgenic mice and in postmortem human HD brain tissue. sCAGs isolated from human HD tissue and then transfected into cells induced toxicity. The pathogenically relevant targets of the sCAGs remain to be determined, but initial experiments suggest several potential transcripts, including ADORA2A and MEIS2 (both reduced in HD brain tissue) and more variably DMPK, ASTN2, and ZFR, all containing either fully or partially complementary CUG and CAG repeats. Determining a more complete list of target sequences, and the extent to which downregulation is necessary or sufficient for toxicity, remain critical issues for further exploration. Curiously, the sCAG species isolated from HD models and human HD brain that induced toxicity were not a homogenous population of RNAs, but were identified in the <100-nt fraction. While cytotoxicity was sCAG-dependent (as toxicity was blocked with anti-sCAG), the relative contribution of sCAGs compared to other miRNAs in the isolated fraction is unknown. Whether Dicer is the only ribonuclease involved in sCAG production also remains to be determined.

It is noteworthy that a DM1 antisense transcript containing the repeat in the CAG orientation is also converted to 21-nt fragments that include CAG units [20], similar to the 21-nt sCAG fragments from the HD locus reported by Banez-Coronel et al. [19]. While the function of the DM1 CAG fragments remains unknown, it was suggested that they may play a role in the abnormal chromatinization at the DM1 locus that occurs in the presence of the expansion mutation [20], raising the possibility that a similar phenomenon may also occur at other loci, such as HD, where sCNG fragments are generated. Both the DM1 and SCA7 antisense transcripts are thought to regulate their complementary sense transcripts [20], [21]. Conversely, the findings in HD by Banez-Coronel et al. suggest that HD sCAG fragments might regulate non-HD CUG- and CAG-containing transcript levels (Figure 1), possibly through an RNA-RNA hybrid mechanism. This may occur through processes similar to the RNA-RNA hybrids formed between the expanded DMPK CUG repeats and the short CAG repeats in CUGBP1 mRNA, proposed to regulate the reduced CUGBP1 mRNA levels in DM1 patient muscles [22].

What regulates the expression of the HTT antisense and sCAG fragments is unknown but may involve epigenetic factors. The expression of the DM1 and SCA7 antisense transcripts are regulated by CTCF binding at sites proximal to the repeat and promoter regions coincident with localized chromatin modifications [20], [21]. Interestingly, CTCF binding also regulates SCA7 CAG instability [23]. The potential role of the HD CTCF site [17], [24] in regulating the expression of HTT or HTT antisense is yet to be determined.

Two recent observations complicate the interpretation of the Banez-Coronel et al. findings [19]. First, homopolymeric polyalanine or polyserine proteins were found to be expressed via a mechanism termed Repeat Associated Non-ATG Translation (RAN) recently described by Zu et al. [25], reviewed in [26]; this raises the possibility that toxic RAN proteins could contribute to the pathogenesis induced by the AUG-free "untranslatable" HTT RNA fragment (Figure 1). Secondly, since the construct used by Banez-Coronel et al. contains the entire HTT exon 1, it is also possible that the recently described antisense HTT transcript is coexpressed with the sense strand transcript [17]. Thus, the long CUG HTT antisense transcript might itself contribute to cytotoxicity, and/or lead to RAN-translated products, and/or influence the process by which sCAGs are generated (Figure 1).

While Banez-Coronel et al. [19] primarily focus on the role of RNAi pathways and the toxicity of sCAGs, it is likely that toxicity induced by HTT sense and antisense RNAs, as in the case of HTT protein, involves multiple pathways, each warranting exploration. For example, what is the pathogenic effect of the aggregation of transcripts containing long CAG or CUG repeats? Might this lead to sequestration or dysregulation of splicing factors, as in DM1? Distinct proteins bind to mRNA containing CAG and CUG repeats—do properties of the transcripts, such as repeat length and the sequence of regions flanking the repeat, modulate this binding? Does the CAG repeat tract length affect transcript stability, or the efficiency of transcription or translation? What is the relationship between CAG expression level and CAG repeat length in inducing toxicity? Does RNA-mediated toxicity provide any clues to selective neuronal vulnerability in HD? Does RAN-translation arise in HD as it does in DM1 and SCA7 patient tissues? These questions demonstrate that every step of the mRNA life cycle in CAG/CTG disease warrants exploration.

Of utmost importance, the findings of Banez-Coronel et al. [19] and others that implicate RNA in HD pathogenesis provide new leads in the search for therapeutic targets. Targeting only the mechanisms induced by expanded polyglutamine tracts may not be sufficient to stop disease pathogenesis. A comprehensive strategy to combat HD will require attention to RNA-mediated toxicity.


The fabrication and characterizations of nanocrystal-ZnO thin film used as active layer of MSM-photodetector structure are reported. The ZnO thin film were successfully sputtered on SiO2/Si substrates without heating or annealing processes by using a novel reactive gas-timing technique. In our experiment, the ZnO thin film properties with different gas-timing ratio of Ar/O2 were investigated. For fabricating of UV detector, the Al interdigitate electrode was deposited on SiO2/Si substrate by DC sputtering process and ZnO thin film was deposited as active layer. The response wavelength peak occurs at around 380 nm corresponding to ZnO energy bandgap of 3.2 eV .The I-V measurements indicates the Schottky behavior of ZnO on Al contact.


The urgency of the problem stated in the article is due to the fact that in connection with the adoption in Russia of the Professional Standard for Teachers, Bachelors of teacher education should be fully ready for the implementation of their professional activities in accordance with the structure and content of labor actions specified in the Standard. The purpose of the article is to present the experience of the teachers of Elabuga Institute of Kazan (Volga region) Federal University in the development of the curriculum module, aimed at the development of the following labor actions: development of skills related to information and communication technologies; formation of common cultural competence and understanding the place of the subject in the overall picture of the world. The leading approach to the study of this problem is the analysis of the existing Bachelor training programs in teacher education, which leads to the conclusion about the need in practice-oriented approach to the training of future teachers. The developed curriculum module is for the discipline "Mathematics and mathematical foundations of information processing", the main purpose of which is to provide students with skills enabling them to master the techniques of search and critical appraisal of natural science information, methods of mathematical processing of the results of educational research, and to involve students in the professional activities beginning with the first year of the study, which will enable them to become highly qualified teachers of the future.


The main aim of this research is to investigate which strategy (Picture Strip Story Strategy or Video Strategy) has more effect on learners' listening comprehension proficiency. The main problems that face EFL learners with regard to listening comprehension relate to the strategies that have been used for listening and the purpose of listening process. Thus, three null-hypotheses are set to investigate the use of picture strip story strategy and video strategy in teaching listening comprehension and their effect on learners' listening comprehension proficiency. A quantitative research design is adopted. The sample (randomly selected) has consisted of (50) participants. They have been divided equally into two groups. The participants study at Department of English, Basic Education College in Mosul University. The content taught which is consisted of (8) videos is chosen from the documentaries of BBC channel. The length of each one is around (5-7) minutes. The same material is edited to suit the group whom taught by using picture strip story strategy. In addition, MCQ test is used for data-collecting. Then, t-test statistic tool is used for analyzing the collected data. Finally, the results reveal that both strategies are useful for teaching listening comprehension. Group (B) who taught by using video strategy has scored (16.4800) which is more than group (A) who taught using picture strip story strategy whom has scored(13.2800).


The 'big new biology' is a vision of a discipline transformed by a commitment to sharing data and with investigative practices that call on very large open pools of freely accessible data. As this datacentric world matures, biologists will be better able to manage the deluge of data arising from digitization programs, governmental mandates for data sharing, and increasing instrumentation of science. The big new biology will create new opportunities for research and will enable scientists to answer questions that require access to data on a scale not previously possible. Informatics will become the new genomics, and those not participating will become marginalized. If a traditional discipline like protistology is to benefit from this big data world, it must define, build, and populate an appropriate infrastructure. The infra- structure is likely to be modular, with modules focusing on needs within defined subject and makes it available in standard formats by an array of pathways. It is the responsibility of protistologists to build such nodes for their own discipline.


Introduction Increased reactive oxygen species (ROS) production is involved in the pathophysiology of cardiac hypertrophy and failure. Interestingly, a specialised ROS-generating enzyme NADPH oxidase-4 (Nox4) was previously found to have beneficial effects by promoting adaptive remodelling during pressure-overload cardiac hypertrophy. Nox4 modulates intracellular signalling cascades but how it achieves beneficial effects in the chronically overloaded heart remains unclear. Methods and results To obtain an unbiased global overview of putative Nox4-mediated changes, the proteome of cardiac-specific Nox4 transgenic (TG) and wild-type (WT) mouse hearts was first characterised through a 2D-DIGE approach. TG hearts had a significant over-representation of changes in protein levels of enzymes involved in glucose and fatty acid utilisation. We therefore analysed the metabolome using 1H-NMR and targeted LC-MS approaches. This identified a differential accumulation of glycolytic intermediates in the proximal part of glycolysis both in unstressed and pressure-overloaded TG hearts, as well as an increase in alanine levels (1.4 fold, p = 0.05), confirming significant alterations to metabolism. To specifically quantify glucose uptake, glycolysis, glucose oxidation and fatty acid oxidation rates, ex vivo working heart studies were conducted. TG hearts had a marked increase cf. WT in palmitate oxidation rate in the unstressed as well as pressure-overloaded heart (3.6 fold increase; n = 6/group; p = 0.01). Glucose uptake was unaltered but glycolysis and oxidation rates were decreased, suggesting diversion of glucose away from oxidation. Importantly, an increase in palmitate oxidation was not detrimental either for in vivo cardiac energetics (31P-NMR) or contractile function during pressure-overload hypertrophy. We found that activity of the hexosamine biosynthesis pathway (HBP), an alternative route for glucose metabolism, was increased in TG hearts as assessed by the O-GlcNAc post-translational modification of cardiac proteins by N-acetylglucosamine, the end-product of HBP. O-GlcNAc levels were 2.4 fold higher in TG cf. WT (n = 4/group; p = 0.02). In cultured cardiomyocytes, endogenous Nox4 induced similar changes in HBP and palmitate oxidation (extracellular flux analysis), and it was found that changes in O-GlcNAcylation regulated fatty acid oxidation. Discussion These results show that Nox4 reprograms substrate utilisation in the heart by directing glucose towards the HBP and inducing a linked increase in fatty acid oxidation. These changes appear to enable the heart to better adapt to chronic pressure overload and may be important in the beneficial effects of Nox4 on cardiac remodelling. These data identify a novel redox mechanism that drives beneficial metabolic reprogramming in the heart and suggest potential new therapeutic approaches to promote adaptation to chronic overload stress.


: This study estimated the induced effects of LNG, mega PV (photovoltaic), small PV, onshore wind and offshore wind power, which will be used as major power sources under the Korea's energy transition policy. The 2015 Input–Output Statistics of Bank of Korea were used to reflect Korea's economic structure. The MCI (manufacture, construction and installation) and O&M (operation and maintenance) of each power source would have different effects, so in the analysis the MCI and O&M of each power source were distinguished. According to estimation results, the induced-effect coefficients of the MCI are greater than those of the O&M in every power source. The induced production effect coefficient of the MCI is decreased in the order of mega PV > small PV > LNG power > offshore wind > onshore wind. The induced production effect coefficient of the O&M is decreased in the order of mega PV > small PV > onshore wind > offshore wind > LNG thermal. The induced employment coefficient of the MCI is decreased in the order of LNG thermal > mega PV > small PV > onshore wind > offshore wind. PV power and wind power have bigger induced effects and bring economic effects in Korean economy. The carbon neutrality and energy transition policies implemented by Korea have a certain level of induced effects and offset the burden of transition costs even if existing power sources are replaced with environmentally friendly power sources.


The main goal of frac monitoring is to obtain a clear definition of event characterization to ultimately compute SRV. Enhancement in signal-to-noise ratio is one of the key elements used to discriminate a successful technique from others. While in the buried sensors design the noise reduction is a wellaccepted advantage, the simple layout of surface sensors arrayis still under discussion. This abstract presents results obtained with a new surface design used in hydraulic fracturation monitoring showing how geometry and spatial distribution of the sensors can improve SNR and therefore sensitivity. This new design is named'patch design'.The name is self-explanatory: OnePatch consists in a given number of sensors closely distributed; a patch design is a series of patches sparsely distributed above the region of interest. This design has several advantages; we will discuss here the economic and technical benefits of this method. Sensor deployment can be easily adapted to the environment optimizing permitting, line clearing, access and avoiding noise prone areas. The economic advantage does not weaken the technical benefit: at the patch scale, the short distance between sensors allowsadvanced summation to optimallypreserve the signal and reduce the noise. The patch design provides a much higher signal-tonoise ratio compared to the usual surface designs. Real cases examples will show how the patch design combines the advantages of both surface and shallow buried array designs.


Background/Aims: The aim of the present study is to evaluate if the intensity of the cardinal symptoms of functional bowel disorders could be used to identify homogenous groups of patients defined by the Rome criteria. Method: In this observational study, 1,729 consecutive outpatients (73% females) filled out the Rome III questionnaire and 10-point Likert scales for constipation, diarrhea, bloating (BL)/distension, abdominal pain (AP) during the week before the medical consultation. A Gaussian mixture model was used for clustering the patients according to the intensity of symptoms without a priori information, and a classification tree was constructed from this clustering. Data were analyzed using analysis of variance and logistic regression analysis. Results: According to the intensity of symptoms, the patients are divided into 8 groups named according to their main symptomatology: "painful constipation" (PFC), "mild pain constipation" (MPC), "painful diarrhea" (PFD), "mild pain diarrhea" (MPD), "mixed transit" (MT), "BL," "AP," and "nonspecific" (NS). The study of the relationship between the Rome III classification and this new grouping shows that irritable bowel syndrome (IBS)-constipation is associated with PFC, IBS-diarrhea with PFD and MPD, SII-mixed with MT, SII-unspecified with BL, functional constipation with PFC and MPC, functional diarrhea with MPD and NS, BL with "BL" and NS, nonspecific functional bowel disorders (FBD) with NS, and functional AP with "BL" and AP (p < 0.01 for all associations). Conclusion: A symptom intensity-based classification of FBD patients could simplify clinical phenotype, give homogeneous groups of patients, and could eventually be used by nongastroenterologists and in clinical research.


Bio-structured carbon was obtained by carbonization of rattan in Ar. Then, the charcoal was reacted with Si at 1500 °C to form SiC. It was also reacted with Si and 2024 aluminum alloy at 1400°C for various times to form composites. The results showed that the SiC was beta phase and had the structure of rattan. SiC whiskers were also found on the inner surfaces of the pore channels (vessels) of rattan structure. The bulk density of the porous SiC was 1.5 g/cm3 and its open porosity was 44%. On the other hand, the charcoal embedded in Si powder and 2024 alloy was converted into SiC/aluminum-silicon composite after heat treatment. The charcoal was reacted to form SiC first. Then, Al-Si alloy infiltrated into the pores of the porous SiC to form composites. When the alloy composition was Al-20 at% Si, the composite obtained after 5 hours of reaction had bulk density of 2.3 g/cm3, open porosity of 19%, compressive strength of 316 MPa and bending strength of 138 MPa.


After using plated CBN hard gear-honing-tools with standard involute tooth profiles, there will be the middle concave errors generally around pitch circle on the machined gear tooth surfaces. For the factors caused to errors are much complicated, it is difficult to calculate them accurately by the analytic method. Therefore, Using Pro/E and ANSYS software, the engaging situation between gear-honing-tool and gear was simulated and analyzed. Based on the results of the analysis, the abrupt changing extent of the compression stress was determined near pitch circle. Along the number of the machined gear teeth was changed, the abrupt changing extent of the compression stress was varied accordingly, which was also coincided with the middle concave errors. Those provided the theoretical foundation for the tooth profile modification of the hard gear-honing-tools, it was proved useful to reduce or eliminate middle concave error in practice.


Nuclear receptors (NRs) are transcription factors whose activity is modulated by ligand binding.These receptors are at the core of complex signaling pathways and act as integrators of many cellular signals. In the last decade our understanding of NRs has greatly evolved. In particular, regulation of NR subcellular dynamics has emerged as central to their activity. Research on the subcellular distribution of the thyroid hormone receptor (TR) has revealed new dimensions in the complexity of NR regulation, and points to the possibility that NR mislocalization plays a key role in oncogenesis. For many years,TR was thought to reside exclusively in the nucleus. It is now known that TR is a dynamic protein that shuttles between the nucleus and cytoplasm.TR is localized to the nucleus in a phosphorylated form, suggesting that compartment-specific phosphorylation mediates cross-talk between multiple cell signaling pathways.The oncoprotein v-ErbA, a viral-derived dominant negative variant of TR is actively exported to the cytoplasm by the CRM1 export receptor. Strikingly, the oncoprotein causes mislocalization of cellular TR and some of its coactivators by direct interaction. Here, we offer some perspectives on the role of subcellular trafficking in the oncogenic conversion of TR, and propose a new model for oncoprotein dominant negative activity.


Recently, several studies have proposed progressive or sequential layer-wise training methods based on the boosting theory for deep neural networks. However, most studies lack the global convergence guarantees or require weak learning conditions that can be verified a posteriori after running methods. Moreover, generalization bounds usually have a worse dependence on the network depth. In this paper, to resolve these problems, we propose a new functional gradient boosting for learning deep residual-like networks in a layer-wise fashion with its statistical guarantees on multi-class classification tasks. In the proposed method, each residual block is recognized as a functional gradient (i.e., weak learner), and the functional gradient step is performed by stacking it on the network, resulting in a strong optimization ability. In the theoretical analysis, we show the global convergence of the method under a standard margin assumption on a data distribution instead of a weak learning condition, and we eliminate a worse dependence on the network depth in a generalization bound via a fine-grained convergence analysis. Moreover, we show that the existence of a learnable function with a large margin on a training dataset significantly improves a generalization bound. Finally, we experimentally demonstrate that our proposed method is certainly useful for learning deep residual networks. Proceedings of the 23International Conference on Artificial Intelligence and Statistics (AISTATS) 2020, Palermo, Italy. PMLR: Volume 108. Copyright 2020 by the author(s).


Some model substrates of the peptidyl transferase centre of E. coli MRE-600 ribosomes were synthesised and tested in a cell-free system without a template. In these substances the nucleic bases were linked covalently with the ribose residue or had a limited rotation about the glycosidic bond. 3'(2')-O-(N-formylmethionyl)-8-bromoadenosine 5'-phosphate and 3'(2')-O-phenylalanyl-8,5'-anhydro-8-mercaptoadenosine were shown to possess a high peptide donor and acceptor activity correspondingly. Contrary to that 3'(2')-O-phenylalanyl-8-bromoadenosine was practically inactive as a peptide acceptor and 3'(2')-O-(N-formylmethionyl)-8,5'-anhydro-8-mercaptoadenosine had no peptide donor activity at all. PMR and CD spectra of the compounds synthesised were investigated. The significance of conformation of the model substrates on their activity is discussed.


Due to the morbidity and lethality of pulmonary diseases, new biomaterials and scaffolds are needed to support the regeneration of lung tissues, while ideally providing protective effects against inflammation and microbial aggression. In this study, we investigated the potential of nanocomposites of poly(vinylidene fluoride-co-trifluoroethylene) [P(VDF-TrFE)] incorporating zinc oxide (ZnO), in the form of electrospun fiber meshes for lung tissue engineering. We focused on their anti-inflammatory, antimicrobial and mechano-electrical character according to different fiber mesh textures (i.e., collected at 500 rpm and 4000 rpm) and compositions: (0/100) and (20/80) w/w% ZnO/P(VDF-TrFE), plain and composite, respectively. The scaffolds were characterized in terms of morphological, physico-chemical, mechanical and piezoelectric properties, as well as biological response of A549 alveolar epithelial cells in presence of lung infecting bacteria. By virtue of ZnO, the composite scaffolds showed a strong anti-inflammatory response in A549 cells, as demonstrated by a significant decrease of interleukin (IL) IL-1α, IL-6 and IL-8 expression in 6 h. In all the scaffold types, but remarkedly in the aligned composite ones, transforming growth factor β (TGF-β) and the antimicrobial peptide human β defensin 2 (HBD-2) were significantly increased. The ZnO/P(VDF-TrFE) electrospun fiber meshes hindered the biofilm formation by S. aureus and P. aeruginosa and the cell/scaffold constructs were able to impede S. aureus adhesion and S. aureus and P. aeruginosa invasiveness, independently of the scaffold type. The data obtained suggested that the composite scaffolds showed potential for tunable mechanical properties, in the range of alveolar walls and fibers. Finally, we also showed good piezoelectricity, which is a feature found in elastic and collagen fibers, the main extracellular matrix molecules in lungs. The combination of all these properties make ZnO/P(VDF-TrFE) fiber meshes promising for lung repair and regeneration.


In this review, we discuss the regulation of ocular blood flow, the role it may play in disease, and the physiologic methods used to assess it. Altered perfusion may play a role in several ocular diseases. In particular, derangements in ocular blood flow have been offered as possible factors in the development of glaucomatous optic neuropathy. In fact, recent studies have suggested that glaucomatous eyes may lack the degree of circulatory autoreg-ulation found in healthy eyes. The autoregulation of ocular blood flow is in response to tissue pressure, myogenic changes, and metabolic levels. To assess the eye's vascular autoregulation, physiologic perturbation of these mechanisms during hemodynamic assessment provides an autoregulatory "stress test." Along these lines, we have refined the technique of altering arterial levels of oxygen and carbon dioxide, thus provoking a metabolic autoregulatory response, during measures of blood velocities in ocular vessels. Using somewhat similar methods, others have documented changes in ocular hemodynamics by altering blood gas levels. Results of our own work suggest that retinal blood flow may be regulated to maintain constant oxygen delivery. Likewise, our studies using carbon dioxide suggest that retinal blood flow may be steeply dependant on Pco2, for these results to be placed in their proper context, future studies directed at better defining normal autoregulation are needed.


The relation between pedestrian flows, the structure of the city and the street network is of central interest in urban research. However, studies of this have traditionally been based on small data sets and simplistic statistical methods. Because of a recent large‐scale cross‐country pedestrian survey, there is now enough data available to study this in greater detail than before, using modern statistical methods. We propose a functional ANOVA model to explain how the pedestrian flow for a street varies over the day based on its density type, describing the nearby buildings, and street type, describing its role in the city's overall street network. The model is formulated and estimated in a Bayesian framework using hour‐by‐hour pedestrian counts from the three European cities, Amsterdam, London and Stockholm. To assess the predictive power of the model, which could be of interest when building new neighbourhoods, it is compared with four common methods from machine learning, including neural networks and random forests. The results indicate that this model works well but that there is room for improvement in capturing the variability in the data, especially between cities.


Abstract Objective Carotid plaque vulnerability assessment could guide the decision to perform endarterectomy. Ultrafast ultrasound imaging (UF) can evaluate local flow velocities over an entire 2D image, allowing measurement of the wall shear stress (WSS). We aimed at evaluating the feasibility of WSS measurement in a prospective series of patients with carotid stenosis. Methods UF acquisitions, performed with a linear probe, had an effective frame rate of 5000 Hz. The flow velocity was imaged over the entire plaque area. WSS was computed with the vector field speed using the formula: with the blood velocity and μ, the blood viscosity. The WSS measurement method was validated using a calibrated phantom. In vivo, WSS was analyzed in 5 areas of the carotid wall: common carotid artery, plaque ascent, plaque peak, plaque descent, internal carotid artery. Results Good correlation was found between in vitro measurement and the theoretical WSS values (R2 = 0.95; p < 0.001). 33 patients were prospectively evaluated, with a median carotid stenosis degree of 80 % [75–85]. The maximum WSS value over the cardiac cycle follows the shape of the plaque with an increase during the ascent, reaching its maximum value of 3.25 Pa [2.26–4.38] at the peak of the plaque, and a decrease after passing of the peak (0.93 Pa [0.80–1.19]) lower than the WSS values in the non-stenotic areas (1.47 Pa [1.12–1.77] for the common carotid artery). Conclusion UF allowed local and direct evaluation of the plaque's WSS, thus better characterizing local hemodynamics to identify areas of vulnerability. Key Points:  Ultrafast vector Doppler allows calculation of the wall shear stress (WSS) by measuring velocity vectors over the entire 2D image. The setup to measure the WSS has been validated in vitro on a linear flow phantom by comparing measurements to in silico calculations. Applying this method to carotid plaque allows us to better describe the hemodynamic constraints that apply along the entire length of the plaque.


We prove that Kilian's four-message succinct argument system is post-quantum secure in the standard model when instantiated with any probabilistically checkable proof and any collapsing hash function (which in turn exist based on the post-quantum hardness of Learning with Errors). This yields the first post-quantum succinct argument system from any falsifiable assumption. At the heart of our proof is a new quantum rewinding procedure that enables a reduction to repeatedly query a quantum adversary for accepting transcripts as many times as desired. Prior techniques were limited to a constant number of accepting transcripts.


A digital hologram is a 2-D recording of the diffraction fringes created by 3-D objects under coherent lighting. These fringes encode the shape and 3-D location information of the objects. By simulating re-lighting of the hologram, the 3-D wave field can be reconstructed and a volumetric image of the objects recovered. Rather than performing object detection and identification in this reconstructed volume, we consider direct recognition of diffraction-patterns in in-line holograms and show that it leads to superior performance. The huge variability of diffraction patterns with object shape and 3-D location makes diffraction-pattern matching computationally expensive. We suggest the use of a dimensionality reduction technique to circumvent this limitation and show good detection and recognition performance both on simulated and experimental holograms.


ABSTRACT The effective integration of educational technologies into early childhood education remains a significant challenge. An important element of this challenge is how practitioner beliefs about pedagogy relate to how digital technologies are used in the early years classroom. Focussing on early childhood practitioner beliefs in relation to pedagogy and digital technologies, this paper reports on a doctoral study where Educational Design Research (EDR) methodology was used to investigate how a technology-focussed intervention might lead to changes in one teacher's approach to integrating digital media into her child-centred pedagogy. The data included reflective discussions over a period of 18 months, video observations of digital media use, and scrutiny of relevant documents. The intervention resulted in a change from the teacher being sceptical about the relevance of digital media for early childhood education to her developing effective strategies to integrate digital media into her child-centred pedagogy. This shift in pedagogic approach was made possible by the teacher changing her beliefs about the value of digital technologies in early education. Findings suggest professional learning should address practitioner beliefs about digital media and early years pedagogy, including providing time and space for teacher reflection.


Distortions of self-experience are critical symptoms of psychiatric disorders and have detrimental effects on social interactions. In light of the immense need for improved and targeted interventions for social impairments, it is important to better understand the neurochemical substrates of social interaction abilities. We therefore investigated the pharmacological and neural correlates of self- and other-initiated social interaction. In a double-blind, randomized, counterbalanced, crossover study 24 healthy human participants (18 males and 6 females) received either (1) placebo + placebo, (2) placebo + lysergic acid diethylamide (LSD; 100 μg, p.o.), or (3) ketanserin (40 mg, p.o.) + LSD (100 μg, p.o.) on three different occasions. Participants took part in an interactive task using eye-tracking and functional magnetic resonance imaging completing trials of self- and other-initiated joint and non-joint attention. Results demonstrate first, that LSD reduced activity in brain areas important for self-processing, but also social cognition; second, that change in brain activity was linked to subjective experience; and third, that LSD decreased the efficiency of establishing joint attention. Furthermore, LSD-induced effects were blocked by the serotonin 2A receptor (5-HT2AR) antagonist ketanserin, indicating that effects of LSD are attributable to 5-HT2AR stimulation. The current results demonstrate that activity in areas of the "social brain" can be modulated via the 5-HT2AR thereby pointing toward this system as a potential target for the treatment of social impairments associated with psychiatric disorders. SIGNIFICANCE STATEMENT Distortions of self-representation and, potentially related to this, dysfunctional social cognition are central hallmarks of various psychiatric disorders and critically impact disease development, progression, treatment, as well as real-world functioning. However, these deficits are insufficiently targeted by current treatment approaches. The administration of lysergic acid diethylamide (LSD) in combination with functional magnetic resonance imaging and real-time eye-tracking offers the unique opportunity to study alterations in self-experience, their relation to social cognition, and the underlying neuropharmacology. Results demonstrate that LSD alters self-experience as well as basic social cognition processing in areas of the "social brain". Furthermore, these alterations are attributable to 5-HT2A receptor stimulation, thereby pinpointing toward this receptor system in the development of pharmacotherapies for sociocognitive deficits in psychiatric disorders.


Background: Stereotypes in medicine have become exaggerated for the purpose of workplace amusement. Our objective was to assess the levels of "dark triad" personality traits expressed by individuals working in different health care specialties in comparison with the general population. Methods: We conducted a prospective, cross-sectional study within multiple departments of a UK secondary care teaching hospital. A total of 248 health care professionals participated, and 159 members of the general population were recruited as a comparison group. We measured 3 personality traits — narcissism, Machiavellianism and psychopathy — through the validated self-reported personality questionnaires Narcissistic Personality Inventory (NPI), MACH-IV and the Levenson Self-Report Psychopathy Scale (LSRP), respectively. Results: Health care professionals scored significantly lower on narcissism, Machiavellianism and psychopathy (mean scores 12.0, 53.0 and 44.7, respectively) than the general population (p < 0.001). Nursing professionals exhibited a significantly higher level of secondary psychopathy than medical professionals (p = 0.04, mean LSRP score 20.3). Within the cohort of medical professionals, surgeons expressed significantly higher levels of narcissism (p = 0.03, mean NPI score 15.0). Interpretation: Health care professionals expressed low levels of dark triad personality traits. The suggestion that health care professionals are avaricious and untrustworthy may be refuted, even for surgeons.


We show stable modes (stationary self-trapped beams) of elliptic cross section in an elliptic-core nonlinear fiber. These stable modes can be tapered in the presence of absorption or gain. Ellipticity of the beam can be controlled by induced tapering. Another interesting feature is the possibility of conversion of an elliptic Gaussian laser beam into a circular Gaussian laser beam. A stationary self-trapped beam plus an elliptic-core nonlinear fiber form an elliptic-core linear fiber for a low-power signal beam, and hence one can induce an elliptic-core linear fiber of optically tunable parameters for a low-power signal beam.


Increased physical activity is needed to help persons with disabilities gain access to its benefits. Using Raymore's (2002) framework for understanding facilitators to leisure, this study explored facilitators to physical activity among adults with disabilities. Interviews with 14 adults with disabilities who were determined to be physically active through recreation or sport were conducted. Direct content analysis of respondents' narratives revealed 10 facilitating themes: inclination toward physical activity, personal agency, self-regulation, support of groups and individuals, connectedness to the disability community, enjoyment, opportunities, resources, positive community attitudes, and incentives. Ideas for applying study findings to therapeutic recreation are offered and additional evidence for the value of strengths-based practices is revealed.


The recent emergence of the SARS-CoV-2 in China has raised the spectre of a novel, potentially catastrophic pandemic in both scientific and lay communities throughout the world. In this particular context, people have been accused of being excessively pessimistic regarding the future consequences of this emerging health threat. However, consistent with previous research in social psychology, a large survey conducted in Europe in the early stage of the COVID-19 epidemic shows that the majority of respondents was actually overly optimistic about the risk of infection.


Cyclogenesis is a key forecast challenge at operational forecasting centers such as WPC and OPC, so these centers have a particular interest in unique products that can identify key storm features. In some cases, explosively developing extratropical cyclones can produce hurricane force, non-convective winds along the East Coast and north Atlantic as well as the Pacific Ocean, with the potential to cause significant damage to life and property. Therefore, anticipating cyclogenesis for these types of storms is crucial for furthering the NOAA goal of a "Weather Ready Nation". Over the last few years, multispectral imagery (i.e. RGB) products have gained popularity among forecasters. The GOES-R satellite champion at WPC/OPC has regularly evaluated the Air Mass RGB products from GOES Sounder, MODIS, and SEVIRI to aid in forecasting cyclogenesis as part of ongoing collaborations with SPoRT within the framework of the GOES-R Proving Ground. WPC/OPC has used these products to identify regions of stratospheric air associated with tropopause folds that can lead to cyclogenesis and hurricane force winds. RGB products combine multiple channels or channel differences into multi-color imagery in which different colors represent a particular cloud or air mass type. Initial interaction and feedback from forecasters evaluating the legacy Air Mass RGBs revealed some uncertainty regarding what physical processes the qualitative RGB products represent and color interpretation. To enhance forecaster confidence and interpretation of the Air Mass RGB, NASA SPoRT has transitioned a total column ozone product from AIRS retrievals to the WPC/OPC. The use of legacy AIRS demonstrates future JPSS capabilities possible with CrIS or OMPS. Since stratospheric air can be identified by anomalous potential vorticity and warm, dry, ozone-rich air, hyperspectral infrared sounder ozone products can be used in conjunction with the Air Mass RGB for identifying the role of stratospheric air in explosive cyclogenesis and hurricane force wind events. Currently, forecasters at WPC/OPC are evaluating the Air Mass RGB imagery in conjunction with the AIRS total column ozone to aid forecasting cyclogenesis and high wind forecasts. One of the limitations of the total ozone product is that it is difficult for forecasters to determine whether elevated ozone concentrations are related to stratospheric air or climatologically high values of ozone in certain regions. To address this limitation, SPoRT created an AIRS ozone anomaly product which calculates the percent of normal ozone based on a global stratospheric ozone mean climatology. With the knowledge that ozone values 125 percent of normal and greater typically represent stratospheric air; the anomaly product can be used with the total column ozone product to confirm regions of stratospheric air on the Air Mass RGB. This presentation describes the generation of these products along with forecaster feedback concerning the use of the AIRS ozone products in conjunction with the Air Mass RGB product for the unique forecast challenges WPC/OPC face. Additionally examples of CrIS ozone and anomaly products will be shown to further demonstrate the utility and capability of JPSS in forecasting unique events.


Extreme variation in rainfall distribution during the summer monsoon often results in water stress conditions which affects crop yields. Field experiments were conducted during 2001 and 2002 in rainfed foothill region of North-West India to evaluate different tillage and mulching practices in relation to in-situ soil moisture conservation and productivity of rainfed maize. Soil moisture storage increased to the tune of 2.25, 4.01, and 10.77% at 60 days after sowing (DAS) with shallow tillage, deep tillage, and ridge and furrow sowing treatment over the farmers' practice. The application of mulch on the whole-covered plot resulted in 48.4, 61, and 138% higher soil moisture content at 40, 60, and 80 DAS, respectively. An increase of 18.2, 33.1, and 49.9% in plant height was observed with shallow tillage, deep tillage, and ridge and furrow sowing treatment over farmers' practice. It was also observed that fully-covered plots had 156% higher dry matter yield of maize compared to unmulched plots. There was a 10.6% increase in maize grain yield in ridge and furrow sowing over the farmers' practice. Mulch spread on the whole plot increased the grain and straw yield of maize by 58.6 and 35.0% compared to unmulched control. Grain and straw yield in partial-covered and strip application of mulch was significantly higher by 30.0 and 28.3% and 31.4 and 25.3%, respectively, than in no-mulching treatments. The results can usefully be employed to optimize the use of available mulch and appropriate tilling for improving maize productivity.


A relationship of residual stress distribution and surface molding states on polymeric materials is presented in thin-walled injection molding. The residual stress is computed by computational numerical analysis, observed with stress viewer and birefringence. The residual stress on polymeric parts can allude the surface quality as well as flow paths. The residual stress distribution on polymeric parts is related with thickness, gate layout, and polymer types. Molecular orientation on polymeric parts is also important in thin wall injection molding. The residual stress and molecular orientation are related to the surface molding states intimately. Analysis of the residual stress is validated through photo-elastic method and surface molding states..


The immunoglobulin G (IgG)–containing B lymphocyte antigen receptor (IgG-BCR) transmits a signal distinct from that of IgM-BCR or IgD-BCR, although all three use the same signal-transducing component, Igα/Igβ. Here we demonstrate that the inhibitory coreceptor CD22 down-modulates signaling through IgM-BCR and IgD-BCR, but not that through IgG-BCR, because of the IgG cytoplasmic tail, which prevents CD22 phosphorylation. These results suggest that the cytoplasmic tail of IgG specifically enhances IgG-BCR signaling by preventing CD22-mediated signal inhibition. Enhanced signaling through IgG-BCR may be involved in efficient IgG production, which is crucial for immunity to pathogens.


The quantum-confined Stark effect in intersublevel transitions present in quantum-dots-in-a-well (DWELL) detectors gives rise to a midIR spectral response that is dependent upon the detector's operational bias. The spectral responses resulting from different biases exhibit spectral shifts, albeit with significant spectral overlap. A postprocessing algorithm was developed by Sakoglu that exploited this bias-dependent spectral diversity to predict the continuous and arbitrary tunability of the DWELL detector within certain limits. This paper focuses on the experimental demonstration of the DWELL-based spectral tuning algorithm. It is shown experimentally that it is possible to reconstruct the spectral content of a target electronically without using any dispersive optical elements for tuning, thereby demonstrating a DWELL-based algorithmic spectrometer. The effects of dark current, detector temperature, and bias selection on the tuning capability are also investigated experimentally.


We synthesized a new series of layered copper oxytellurides Sr2TMCu2Te2O2 with variation in transition metal (TM = Mn, Co, and Zn) elements. These compounds are the first example having alternately stacked anti-fluorite Cu2Te2 and perovskite-like TM-oxide layers. Owing to the longer ionic radius of Te compared to those of Se and S, they exhibit larger lattice parameters than isostructural sulfides and selenides. First principles band structure calculation for the Zn compound as a representative reveals a semiconducting direct band gap of ∼1.7 eV and the Co compound shows a comparable band gap in the diffuse reflectance measurement result. From the thermoelectric property study, we determined a power factor of ∼70 μW m−1 K−2 and a figure of merit ZT of ∼0.045 at 770 K for the Co compound, which encourages further improvement in thermoelectric response by applying various enhancement methods. In terms of the magnetic properties, a signature of antiferromagnetic order is observed in the Co and Mn compounds. The present results not only highlight the structural flexibility of the system to tune the physical properties but also suggest that the replacement of the blocking layer can be a new way to improve the thermoelectric performance of layered copper oxychalcogenides.


Background: The Study of Jamu Registry has been done, which is an observational longitudinal study to record the treatment of herbal medicine by physician practices. Respondents are a network of physicians who practice herbal medicine as complementary services. Methods: As researchers did not introduce any interventions, the study is basically observational study. Result: From patient's jamu medical data records, wich is delivered to Registry Center, there were 1452 patients visited, divided into 908 initial visits and 544 follow-up visits. The most USAge of the modalities was jamu (63.5%), followed by combination of jamu and conventional drug (22.26%) and jamu combined body-based therapy (5.2%). Assessment holistic therapy can be enhanced by the patient's symptoms (anamnesis) and scores of Quality of Life (QoL) on the second visit (372 patients). There were a decrease of all the symptoms, the most decrease was common symptom (30%), respiratory tract (21.3%), musculoskeletal (15.5%), neurological (11.4%), gastrointestinal (10.2%), cardio vascular (1.5%) and urinary tract symptoms (3.8%). Based on the modalities given to the patient, who stands out is that the administration of jamu, lowering the general, musculoskeletal and neurological symptom. The combination of herbal medicine and conventional drug lowers the common and neurological symptom. Improvement of Quality of life patients can described as Qol "improved" category rising 20.1%, Qol "settled" category decreased 20.0% and "worsten" category decreased 1%. Conclusion: Based on type of modality used, there was increasing the value of improved QoL categories, respectively: the combination of herbal and conventional drugs, a combination of herbs and body based therapy, and combination jamu, body based therapy and conventional drugs. Recommendation: improvement of holistic therapy in the registry jamu can be used as a baseline formula of jamu, which can be developed for clinical observational studies or clinical trials.


This paper focuses on funds of funds (FOFs) as a form of financial intermediation in private equity (both buyout and venture capital). After accounting for fees, FOFs provide returns equal to or above public market indices for both buyout and venture capital. While FOFs focusing on buyouts outperform public markets, they underperform direct fund investment strategies in buyout. In contrast, the average performance of FOFs in venture capital is on a par with results from direct venture fund investing. This suggests that FOFs in venture capital (but not in buyouts) are able to identify and access superior performing funds.


Introducing optical inter-satellite links in a global navigation satellite system enhances orbit determination and offer frequency synchronization across the constellation. To show proof-of-concept and system capabilities a laboratory demonstrator has been developed and first tests in laboratory environment have been taken out. The demonstrator is buildup of two reciprocal units interconnected via bi-directional free-space optical links. Each unit is composed of opto-mechanical terminal, optical communication system and digital signal processing implemented on a field programmable gate array. Ranging and time transfer is realized utilizing a 25.55 Gigachip-per-second binary phase shift keying modulation scheme. Correlating the received ranging sequence with a local generated reference, pseudo range determination within the order of 100 µm accuracy is achieved. In addition, a 50 Megabit-per-second data signal is multiplexed onto the ranging sequence for exchanging satellite and time information as well as user data. Frequency transfer is realized using a cavity stabilized laser as carrier transferring its stability onto the phase locked local oscillator at the receiver side. Global synchronization at system level is achieved by means of synchronizing the optical carrier and spread sequence to a highly stable clock reference as well precise ranging and information distributed through the data channel. Using on-satellite ultra-stable optical oscillator and a frequency comb for radio frequency reference generation short-term frequency stability in the order of 10-15 s/s (Allan deviation at 1 s gate time) is achieved. The aim of this paper is to show the current status of the laboratory demonstrator development and present first measurements of the entirely setup system. A general overview of the digital signal processing is given and data transmission as well as time transfer are discussed in particular. The laboratory demonstrator setup and mechanical construction is presented. Clock stability transfer between high-accuracy radio frequency reference and the digital signal processing system is shown. Further, optical frequency transfer experiments are performed demonstrating successful synchronization between laboratories.