Background: Type 2 diabetes mellitus (T2DM) and thyroid dysfunction (TD) often present together and complicate each other at many levels. Methodology: In this prospective study, we determined the prevalence of TD among 700 patients with T2DM attending the diabetes clinic of a tertiary care hospital who were recruited. Various sociodemographic factors such as age, gender, marital status, literacy status, and habits and clinical profile were assessed. Results: In all, 68% of male and 31% of female patients were enrolled in this study. About 33.5% of males and 66.4% of females were found with TD. One hundred and fifty-two (21.7%) patients were having TD. Diabetes and TD were more common among females, with advancing age, 45–70 years, sedentary, overweight patients and having familial history. Twenty-five percent of the patients were having prehypertension. About 10.5% of the patients were suffering with hyperthyroidism and 9% were suffering from subclinical hyperthyroidism. Forty-two percent were suffering from hypothyroidism, while 36% had subclinical hypothyroidism. Ten percent had higher T3 hormone levels, 11% had higher T4 hormone levels, and 69% had increased thyroid-stimulating hormone levels. Three percent of patients with diabetes and TD were having cardiovascular diseases. Conclusions: Out of 700 patients with T2DM, 21% were having different kinds of TD. More females with advancing age and sedentary lifestyle were having TD. Screening for TD among diabetes patients could improve case detection and early treatment, indirectly leading to better thyroid-specific treatment outcomes and prevention of DM complications.


Bioinspired strategies have drawn much attention for designing intelligent hydrogels with promising performance. Herein, we present a bioinspired adhesive hydrogel driven by adenine and thymine, which are the basic units of DNA. The adhesive hydrogel exhibited promising adhesive property for the surface of various solid materials, including muscle tissues, plastics, rubbers, glasses, metals, ceramics, carnelians, and woods. The maximum peeling strength of hydrogels was 330 N m-1 on aluminum, superior to that of PAAm hydrogels with 70 N m-1. The strong adhesive behavior remained more than 30 times repeated peeling tests. Moreover, the swelling behavior, morphological structure, mechanical strength, and peeling adhesive strength were also investigated and confirmed the formation and various characteristics of adhesive hydrogels driven by adenine and thymine. Thus, the biomimetic strategy to design promising adhesive hydrogels can provide various opportunities in tissue engineering, such as wound dressing, bioglues, and tissue adhesives.


Actigraphy is a useful tool in the measurement of sleep, with many applicable variables that indicate the quality of a study participant's sleep. Typical actigraphy derived variables from sleep studies include sleep efficiency, sleep la- tency, total sleep time, and the number of nightly awakenings. Actigraphy can also give parameters for autocorrelation and sinusoidal fitting that are used in circadian rhythm modeling. All of these variables are useful in inferential statistics to determine differences between groups. However, no work has been done that examines a set of relationships among these various sleep variables, which can possibly reduce the dimension of the set into a smaller number of interpretable la- tent factors, which can aid in characterizing sleep quality. Factor analyses and structural equation modeling were used to assess how these measured sleep variables load into different factors. Analyses showed that these variables load into 3 factors: sleep time, sleep activity and circadian rhythm.


The K-ras gene is one of the most commonly mutated genes in cancer. The ras proteins act as functional switches in the activation of the MAPK pathway in a complex signaling network coupling growth factor receptors to the intracellular kinases. Mutations in the K-ras gene lead to the constitutive activation of the protein and consequently of the MAPK pathway. K-ras mutations are early events in colorectal carcinogenesis and are observed in 30-40 % of the colorectal cancers. Mutations mostly occur at codons 12, 13 and 61 of the gene and result in the deregulation of the protein activity. Several studies have shown that patients with K-ras mutations do not benefit from therapies with anti-EGFR monoclonal antibodies. miRNAs are global regulators of gene expression by binding to the 39-untranslated region of the target mRNA. Recently, it has been shown that the K-ras gene is regulated at the translational level by binding of the let-7 miRNA. The let-7 family of miRNAs is known to play an important role in several cancer types. A germline SNP at the 39-UTR of the K-ras gene (rs: 61764370 T-G) has been shown to disrupt binding of the let-7 molecule to K-ras resulting in overexpression of the gene and was found to confer increased susceptibility for distinct cancer types. The let-7 miRNA variant was found to be associated with poor outcome in lunh and head and neck cancers. However, the frequency and association of this variant with other cancer types has not been investigated widely. In this study we evaluated the frequency of the K-ras gene variant in 145 patients with colon cancer and 85 healthy individuals and its possible association with the K-ras gene mutations. The K-Ras gene variant was analyzed by polymerase chan reaction-restriction fragment length polymorphism (PCR-RFLP) analysis, K-ras gene mutations were investigated by real time-PCR. The results were evaluated using the Chi-square test. The variant allele of the K-ras gene was observed in 23 patients (15.9%) in the heterozygote form. A single patient was homozygous for the variant allele. The variant allele was detected in 12 % of the control group. K-ras gene mutations were present in 46 (32 %) of the patients. The frequency of the variant allele was 13 % among the patients harboring a K-ras gene mutation. The distribution of the variant allele is in accordance with a report on the US control population and no significant difference was observed between the patients and the controls. Citation Format: Nejat Dalay, Zubeyde Yalniz, Orkun Gurbuz. The K-ras let-7 miRNA binding site variant and K-ras mutations in colon cancer. [abstract]. In: Proceedings of the AACR Special Conference on RAS Oncogenes: From Biology to Therapy; Feb 24-27, 2014; Lake Buena Vista, FL. Philadelphia (PA): AACR; Mol Cancer Res 2014;12(12 Suppl):Abstract nr A48. doi: 10.1158/1557-3125.RASONC14-A48


These days, huge consideration is being given to IOT in many fields. It chiefly manages the correspondence between a few electrical gadgets. The IOT is encountering quick reception in the public, from mechanical to home applications. We can influence gadgets to convey through an interconnection organize. We can apply IOT in many fields. Here, we are for the mostly focusing on controlling Home Machines. As per condition, consequently, the gadgets can do their errands. With the improvement of the social economy, a number of machines which always increases have been exhibited in a house. It is an issue that how to oversee and control these apex different machines proficiently and advantageously in order to accomplish more agreeable, security and solid space at home. In current Venture, We will manage a few parts of the IOT in Home Machines controlling.


OBJECTIVE
Maternal serum placenta growth factor levels have been shown to be significantly reduced in women with established preeclampsia. However, the temporal change in serum placenta growth factor levels before the clinical onset of preeclampsia is not known.

STUDY DESIGN
Serum samples were collected from patients at the first prenatal (5-15 weeks' gestation), second-trimester (16-20 weeks' gestation), and third-trimester (26-30 weeks' gestation) visits. Serum placenta growth factor levels were determined and analyzed according to pregnancy outcome.

RESULTS
Maternal placenta growth factor levels during normal gestation increased dramatically from the first to the third trimester. At the same gestational time points, in contrast, significantly lower serum placenta growth factor levels were found in patients in whom mild or severe preeclampsia eventually developed (P <.01). Low maternal serum placenta growth factor levels during early gestation were associated with a significant odds ratio for development of preeclampsia (P <.005).

CONCLUSION
Relatively decreased levels of serum placenta growth factor occur before the onset of clinical preeclampsia, which suggests that placenta growth factor measurement could be used to discriminate those pregnancies predisposed to development of preeclampsia.


— The design of a wireless LPG leakage monitoring system is proposed for home safety. The aim of this paper is to monitor for LPG leakage to avoid fire accidents providing house safety feature where security has been an important issue and alerts the consumer about the leak by SMS and as an emergency measure the system will turn off the power supply, while activating the alarm. In this paper we proposed the additional advantage of the system is that it continuously monitors the level of the LPG present in the cylinder using load sensor and if the gas level reaches below the threshold limit of gas around 2kg so that the user can replace the old cylinder with new in time and automatically books the cylinder using a GSM module. The device ensures safety and prevents suffocation and explosion due to gas leakage. We have also included DC battery in the system to operate even when the power goes off due to the power cut.


Type III neuregulins exposed on axon surfaces control myelination of the peripheral nervous system. It has been shown, for example, that threshold levels of type III β1a neuregulin dictate not only the myelination fate of axons but also myelin thickness. Here we show that another neuregulin isoform, type III-β3, plays a distinct role in myelination. Neuronal overexpression of this isoform in mice stimulates Schwann cell proliferation and dramatically enlarges peripheral nerves and ganglia—which come to resemble plexiform neurofibromas—but have no effect on myelin thickness. The nerves display other neurofibroma-like properties, such as abundant collagen fibrils and abundant dissociated Schwann cells that in some cases produce big tumors. Moreover, the organization of Remak bundles is dramatically altered; the small-caliber axons of each bundle are no longer segregated from one another within the cytoplasm of a nonmyelinating Schwann cell but instead are close packed and the whole bundle wrapped as a single unit, frequently by a compact myelin sheath. Because Schwann cell hyperproliferation and Remak bundle degeneration are early hallmarks of type I neurofibromatosis, we suggest that sustained activation of the neuregulin pathway in Remak bundles can contribute to neurofibroma development.


High-entropy alloys (HEAs) consisting of multiprincipal elements have demonstrated many interesting structural, physical, and chemical properties for a wide range of applications. This article is a review of the current theoretical research on the elastic parameters of HEAs. The performance of various ab initio-based computational models (effective medium and supercell approaches) is carefully analyzed. Representative theoretical elastic parameters of different HEAs, including single-crystal elastic constants, polycrystalline elastic moduli, elastic anisotropy, and Debye temperature, are presented and discussed. For comparison, simple mixtures of the elastic moduli of pure elements are calculated and contrasted with the ab initio results. The present work provides a reference for future theoretical investigation of the micromechanical properties of systems based on HEAs.


This paper assessed the effects of housing market shocks on real output in South Africa over the period 1969Q4 – 2014Q4, by emphasizing the real private consumption channel. The agnostic identification procedure employed in this paper has delivered impulse responses that are overall consistent with the existing literature. The paper appropriately identified housing market shocks as non-monetary housing demand shocks. 20% of the variation in house prices are explained by the housing market shocks. The effects of housing demand shocks on real private consumption are short-lived, explaining why real output responded transitorily to these shocks. Housing demand shocks have managed to explain nearly 13% and 14% variations in real private consumption and real output, respectively, over 20-quarters ahead forecast revision.


The increasingly more stringent performance and power requirements of Internet routers call for scalable IP lookup strategies that go beyond the currently viable TCAM- and trie-based solutions. This paper describes a new hash-based IP lookup scheme that is both storage efficient and high performance. In order to achieve high storage efficiency, we take a multi-hashing approach and employ an advanced hashing technique that effectively resolves hashing collisions by dynamically migrating IP prefixes that are already in the lookup table as new prefixes are inserted. To obtain high lookup throughput, the multiple hash tables are accessed in parallel (using different hash functions) or in a pipelined manner. We evaluate the proposed scheme using up-to-date core routing tables and discuss how its key design parameters can be determined. When compared with state-of-the-art TCAM designs, our scheme reduces area and power requirements by 60% and 80% respectively, while achieving competitive lookup rates. We expect that the proposed scheme scales well with the anticipated routing table sizes and technologies in the future.


The objective of the present work was to develop indications for the combined treatment of patients presenting with osteoarthrosis including the use of peloid applications and intramuscular injections of alflutop. The study was based at Yakty-Kul' health resort and included 94 patients at the age from 40 to 59 years. The proposed method was shown to have beneficial effect on the patients' clinical conditions. In addition, the treatment caused a decrease in the level of tumour necrosis factor-alpha (TNF-alpha) that turned out to be related to the articular index.


We present the case of a 93-year-old patient with intestinal occlusion due to a descending colon tumor, with carcinomatous ascites and secondary liver and lung determinations. Considering the risks associated with a surgical act in such a patient and the impossibility of performing a curative intervention, a self-expanding metallic colonic stent was mounted. The post-intervention evolution was favorable, the patient being discharged 48 hours later. Left colon cancer is diagnosed in the occlusive phase in 8 to 26% of cases (1). It often requires an immediate surgical resolution due to the potential risk of death. Emergency surgery involves increased rates of morbidity and mortality (2). Thus, other ways of resolving these surgical emergencies have been developed. Colonic stents were first reported in the literature by Dohmoto (3). Initially, the use of stents was as the final method of palletising (4). Later, they were used as a bridge to minimally invasive programmed surgery (5).


produced by a wide range of microbes as a source of energy for metabolism, carbon, and oxidoreduction; since they exhibit some properties, which are remarkably similar to those of polyolefins derived from fossil fuels. The literature review conducted over the past decade reveals that polyhydroxybutyrate (PHB) has the potential physical qualities for food packaging material, single-use plastic goods and medicinal sectors. Polyhydroxybutyrate (PHB) is a bacterial biopolymer that has begun to replace petrochemical plastics due to the present trend towards the efficient utilisation of relatively cheaper substrates for its production. This review discusses explicitly the developments in the analysis of microbial biopolymer PHB and additionally provides an outline of current industrial applications, Production, Extraction methods, genes involved, microbes that are capable of producing PHB, challenges faced during production and degradation of PHB.


Radio frequency identification (RFID) provides great potential for different Internet of Things (IOT) applications. In the future, material choices in these IOT devices will have a huge effect on the environment and thus use of renewable materials is a growing trend. In this paper, passive ultra high frequency (UHF) RFID tags were inkjet-printed directly on wood, paper, and cardboard substrates, and their performance was evaluated by measuring two key properties: threshold power and theoretical read range. According to our measurements, the tags on wood showed read ranges of 7 - 8 meters, the tags on cardboard exhibited read ranges of 4 - 7 meters, and the tags printed on paper showed read ranges of 2 - 7 meters through the global UHF RFID band. According to these results, the performance of these inkjet-printed UHF RFID tags is sufficient for many IOT devices and potential applications e.g. in construction and packaging industry.


This study provides a combined theoretical and experimental analysis of the far-field (extinction) and of the near-field (SERS enhancement) spectral distribution in hollow nanoparticles, that is, silver-gold nanocages (NCs). Chitosan protected NCs have been synthesized by a galvanic replacement-based procedure: their morphological properties and chemical composition have been characterized by TEM, STEM and ICP. NCs were then functionalized with a thiolated organic dye prior to carrying out SERS measurements. Finite Element Method simulations of a single NC have shown that the field enhancement at the excitation wavelength follows the same spectral dependence as the extinction spectrum and, consequently, the SERS enhancement profile, as a function of the excitation wavelength, peaks at higher energy with respect to extinction. The simulated extinction is remarkably narrower than the experimental spectrum of NCs in solution, indicating that the colloidal sample is substantially polydispersed. However, a simple qualitative model that we have developed would suggest that the SERS enhancement profile is blue-shifted with respect to the extinction in the presence of polydispersivity as well. In addition, NC dimers have been simulated: both their extinction and near field-spectra shift to the red when the size of the gap is reduced analogous to what happens with dimers of filled spherical nanoparticles (NPs). In addition, simulations also revealed that a NC dimer is only slightly more efficient in amplifying the field with respect to the isolated NC, and this behavior is peculiar to NCs. In fact, filled spherical NP dimers exhibit a remarkably stronger field enhancement with respect to the isolated NP. By means of Wavelength Scanned SERS, we measured the spectral distribution of the local field in a dispersion of NCs. We observed experimentally that the local field is distributed in the same spectral region as the extinction and that the absolute value of the SERS enhancement factor maintains a low value throughout the range explored (568-800 nm). We propose that the observed correlation between the SERS profile and the extinction is accidental and originates from the limited increase in amplification provided by NC aggregates with respect to isolated NCs.


The origin of the low-frequency noise in graded- channel silicon-on-insulator nMOSFET is studied as a function of the back-gate bias at a low drain-to-source bias. It is shown that an excess noise peak that is correlated with the peak in the transconductance can be observed. This excess noise is due to a generation-recombination component in the low-frequency range, which is suppressed when the back gate is in accumulation mode.


Although mucocele of the frontal sinus was not dealt with as a problem in therapeutics in authoritative medical literature earlier than the eighteenth century, this pathologic condition must have existed in ancient times. An interesting bit of writing indicating this is the description by Boenninghaus 1 of a skull discovered by him among the thousands ornately arranged on the walls of the famous chapel at Tscherbeney, built entirely of human bones. Boenninghaus made a careful examination of this skull. He found the bone structure large and strong, with the teeth for the most part absent; the skull appeared to be that of a person of middle age. The cranial capsule was perfectly preserved. A large part of the anterior wall of the frontal sinus was absent. In the cerebral wall of the left frontal sinus was a roundish defect, approximately 1 cm. in diameter. From these and other observations Boenninghaus concluded


Neocarzinostatin, an antineoplastic agent which is effective against human leukemia, induced unscheduled DNA synthesis in human leukemic leucocytes. This indicated the existence of repair process against at least a part of DNA damage caused by the agent. The extent of unscheduled DNA synthesis increased in parallel with the concentration of Neocarzinostatin up to 5 microgram/ml, followed by a decline at more than 5 microgram/ml. Leucocytes from patients with chronic myelogenous leukemia had higher repair synthesis after Neocarzinostatin treatment compared to those from patients with acute leukemia. The amount of repair synthesis correlated well with the proportion of immature leucocytes among chronic myelogenous leukemia samples, but such correlation was not found among acute leukemia samples.


The inactivation rate of foodborne microorganisms under high hydrostatic pressure (HHP) is influenced by factors such as substrate, species, strain, temperature, pH, and stage of growth of the cell. In this study, 445 D(P)-values from previously published data were analyzed, including those from bacterial spores, vegetative cells, and yeasts. Three secondary linear inactivation models with pressure and/or temperature as process parameters were tested to estimate global log D(P)-, z(P)-, and z(T)-values, and the influence of these parameters and additional factors was assessed. The results show that significant differences in microbial resistance are mainly the result of temperature, highlighting the need for its inclusion as a process parameter. Perhaps due to the large number of data and very distinct factors, the remaining factors showed no significant differences in microbial resistance, except in the case of Clostridium spp. in soy milk, which showed decreased resistance in this substrate compared with its behavior in other products. These results serve to establish priorities among factors influencing HHP inactivation and to estimate global kinetic parameters as a basis for setting target levels of inactivation. Moreover, they can be used as a benchmark for comparison of microbial HHP inactivation data gathered in future studies.


As the title suggests, this small book attempts to give thinking people guidance in an effort to work their way through the idealogical confusion engendered by the present world crisis. In the spirit of Hegel it presents a philosophical synthesis of conflicting social views which now possess the minds of men. Believing that conflict and competition are normal social processes which must always be reckoned with, the author suggests that mankind today faces two basic alternatives: annihilation through atomic and biological warfare or some sort of compromise of existing issues. Possessing a progressive view of history, he thinks that the second alternative is the one which will prevail. Therefore, he discusses ways and means through which it may be implemented. He concludes that the United Nations organization provides the most adequate framework through which the necessary compromises may be effected. He hopes that the time will come when all national groups will be united in a world state, under one central government. But he thinks that this can be best achieved when differences between nationalities, ideologies, and regional cultures are frankly recognized and properly delineated in a harmony of the whole. This book is very thought-provoking. It is highly theoretical in approach. But sound theory is necessary to sound practice. Moreover, it challenges the accepted categories of thinking and acting. But it points out how the values inhering in them may be preserved in a new era of world society. Millard R. Brown


With a multitude of departmental information systems, executives find it difficult to make well-informed decisions affecting cost or to change physician behavior. A well-conceived EIS is alleviating such difficulties at many organizations.


Background : All over the world, women experience unwanted pregnancy and some of them seek to terminate the pregnancy and undergo induced abortion. In Ethiopia, abortion is still common and it is one of the contributing factors for maternal death. In 2008 it was estimated that, there were 382,000 induced abortions in Ethiopia and 52,600 women were treated for complications of abortion. Most of these women who tend to experience induced abortion are adolescents and youth with age below 25 years. The aim of this study was, to assess the magnitude of induced abortion and associated factors among Wachamo University regular female students. Methods : A cross sectional study design was used. Data were collected from 461 randomly selected female students of Wachamo University by using pre-tested structured questionnaire from January to March, 2015. The collected data were entered using EPI info Version 3.5.1 and analyzed by SPSS version 16. Descriptive statistics was computed and odds ratio along with the 95% confidence interval was estimated to identify factors associated with induced abortion using multivariate logistic regression. Level of statistical significance was declared at P- value less or equal to 0.05. Results: In this study the prevalence of induced abortion was 5.9% (95% CI 3.8-8.0%), from which 9(33.3%) were conducted in an unsafe conditions. A total of 180(39 %) female students had sex and 58 (12.58%) of them get pregnant. Out of the total pregnancies, 53(91.4%) were unwanted. Based on the results from multivariate logistic regression, living out of campus [AOR= 6.78, 95% CI: (1.44, 31.97)], Substance use [AOR= 4.75, 95% CI: (1.12, 20.16)], and earning enough pocket money [AOR= 6.91, 95% CI: (1.62, 29.50)] were significantly associated factors with induced abortion. Conclusion and Recommendation : A significant proportion of pregnancies among students in higher educational institution are terminated with induced abortion. Living out of campus, substance use and pocket money have significant association with induced abortion. The university and local health bodies should work together to address for prevention of unintended pregnancy and induced abortion. Key words : Induced abortion, Abortion, Adolescent and youth


There were examined 102 patients with purulent-inflammatory affection of soft tissues after surgical and urological operations. Efficacy of the napkins with metallocomplex application, according to dynamics of the wound surface size and its healing speed, was studied. Comparative analysis of the results of the purulent wound treatment using various local preparations was conducted. The conducted investigation results witness, that the napkins with metallocomplex owe the increased antibacterial activity, influence positively the dynamics of the wound surface size and its healing speed.


The automated rapid sediment analyser (ARSA) is a pressure-transducer grain-size analysis system. This basic Woods Hole-type fall tube was automated by the addition of a digital voltmeter, Hewlett-Packard 9810A calculator, and an x-y plotter. Eight min after sample introduction, the system automatically produces size distribution data in 0·25-φ intervals, distribution statistics, and a plotted frequency histogram.


We propose an interpretation of multiparty sessions with asynchronous communication as Flow Event Structures. We introduce a new notion of global type for asynchronous multiparty sessions, ensuring the expected properties for sessions, including progress. Our global types, which reflect asynchrony more directly than standard global types and are more permissive, are themselves interpreted as Prime Event Structures. The main result is that the Event Structure interpretation of a session is equivalent, when the session is typable, to the Event Structure interpretation of its global type.


The on-line nanoscale coupling of a surface plasmon resonance (SPR)-based inhibition biosensor immunoassay (iBIA) for the screening of low molecular weight molecules with nano-liquid-chromatography electrospray ionization time-of-flight mass spectrometry (nano-LC ESI TOF MS) for identification is described. The interface is based on a reusable recovery chip (RC) that contains a nanoscale biosorbent composed of a hydrogel layer modified with antibodies raised against the analyte featuring the unique possibility of performance characterization using the SPR biosensor. Various hydrogel chemistries were evaluated, and the standard Biacore CM5 chip showed the highest capture capacity in combination with affinity-purified polyclonal antibodies. The procedure has four stages: the samples are prepared (1) and screened using a screening chip (SC) in the iBIA (2). Suspected noncompliant samples as being noncompliant are reinjected over the RC, and the analyte is captured at subnanogram level (3). The captured analyte is released, and the eluate is analyzed with nano-LC ESI TOF MS via a loop-type interface (4). The coupling of the technologies proved effective for screening enrofloxacin, a model compound, in incurred chicken muscle samples followed by identity confirmation in suspected noncompliant samples. Ciprofloxacin, a known metabolite of enrofloxacin, was identified as well in incurred chicken samples. This demonstrates the potential of the technologies coupled by means of a RC for the rapid screening and identification of known as well as unknown compounds. Finally, we demonstrate the feasibility of combining the two biosensor chips (SC and RC) with a robust chip-based nano-LC chip TOF MS system, thus providing a robust alternative triple-chip system.


Recent years have seen the emergence of programmable metasurfaces, where the user can modify the electromagnetic (EM) response of the device via software. Adding reconfigurability to the already powerful EM capabilities of metasurfaces opens the door to novel cyber-physical systems with exciting applications in domains such as holography, cloaking, or wireless communications. This paradigm shift, however, comes with a non-trivial increase of the complexity of the metasurfaces that will pose new reliability challenges stemming from the need to integrate tuning, control, and communication resources to implement the programmability. While metasurfaces will become prone to failures, little is known about their tolerance to errors. To bridge this gap, this paper examines the reliability problem in programmable metamaterials by proposing an error model and a general methodology for error analysis. To derive the error model, the causes and potential impact of faults are identified and discussed qualitatively. The methodology is presented and exemplified for beam steering, which constitutes a relevant case for programmable metasurfaces. Results show that performance degradation depends on the type of error and its spatial distribution and that, in beam steering, error rates over 20% can still be considered acceptable.


Influenza B virus (IBV) is one of the two major types of influenza viruses that circulate each year. Unlike influenza A viruses, IBV does not harbor pandemic potential due to its lack of historical circulation in non-human hosts. Many studies and reviews have highlighted important factors for host determination of influenza A viruses. However, much less is known about the factors driving IBV replication in humans. We hypothesize that similar factors influence the host restriction of IBV. Here, we compile and review the current understanding of host factors crucial for the various stages of the IBV viral replication cycle. While we discovered the research in this area of IBV is limited, we review known host factors that may indicate possible host restriction of IBV to humans. These factors include the IBV hemagglutinin (HA) protein, host nuclear factors, and viral immune evasion proteins. Our review frames the current understanding of IBV adaptations to replication in humans. However, this review is limited by the amount of research previously completed on IBV host determinants and would benefit from additional future research in this area.


In recent years, the potential for collision between humans and robots has drawn much attention since service robots are increasingly being used in the human environment. A safe robot arm can be achieved using either an active or passive compliance method. A passive compliance system composed of purely mechanical elements often provides faster and more reliable responses to dynamic collision than an active system involving sensors and actuators. Since positioning accuracy and collision safety of a robot arm are equally important, a robot arm should have very low stiffness when subjected to a collision force capable of causing human injury. Otherwise, it should maintain a very high stiffness. To implement these requirements, a novel safe joint mechanism (SJM-III) consisting of an inclined link, a slider with rollers, and linear springs is proposed. The SJM-III has the advantage of nonlinear stiffness, which can be achieved only with passive mechanical elements. Various analyses and experiments on static and dynamic collisions show high stiffness of the SJM-III against an external torque less than a predetermined threshold torque, with an abrupt drop in stiffness when the external torque exceeds this threshold. The safe joint mechanism enables a robot manipulator to guarantee positioning accuracy and collision safety, and which is simple to install between an actuator and a robot link without a significant change in the robot's design.


The PCAOB mandated, over the objections of the large audit firms and others, that for fiscal years ending on or after December 15, 2017, the audit report shall include information about auditor tenure. In this paper we answer the call for academic research about "the impact and usefulness of the auditor tenure disclosure as it becomes implemented" from Franzel (2017). We use data from 2,718 firms in our analyses. We find that in the case of clients with long (short) auditor tenure, the proportion of shareholder votes not ratifying the auditor increased (decreased) after public disclosure of auditor tenure. Thus, it appears that public disclosure of auditor tenure influenced shareholder voting and sensitized shareholders to longer audit tenures.


Given the severity and complexity of the neurologic disorders that can affect infants and children, pediatric neurologists frequently encounter complex and challenging ethical issues. This discussion uses five cases to illustrate common ethical issues and dilemmas that are confronted by pediatric neurologists. These cases involve the provision of artificial nutrition and hydration to patients in vegetative or minimally conscious states, the use of mechanical ventilation for patients with spinal muscular atrophy, controversial therapies for autistic spectrum disorders, the use of medical information obtained over the Internet, and genetic testing in children with suspected Huntington's disease. The ethical concepts discussed in these cases include autonomy, confidentiality, futility, surrogate decision-making, the best-interest principle, and the withholding and withdrawal of treatment.


Cast planning is a practical problem frequently encountered in steel industry. Its task is to group charges into batches (casts) with respect to the similarities of steel-grade and dimensions between charges, taking account of the practical technique constraints on life-span of tundish. Effective cast planning can reduce the changeover cost of charges and enhance the productivity of continuous casters. The objective under our consideration is to minimize the total dissimilarity costs between the charges in the same casts, to minimize the number of casts and the number of unselected charges. A quadratic integer programming model with multiple objectives for this problem is formulated. It is NP-complete, and so an iterated local search (ILS) algorithm is developed for the problem. In this algorithm, cyclic transfer neighborhood is adopted, in which several charges are transferred among casts simultaneously as a manner of cycle. A new kick strategy is developed with the idea of assigning charges to different casts according to the dissimilarity costs between them and the casts' central charges identified by the current solution. Computational results using real data from an advanced iron & steel company in China indicate that the ILS algorithm provides optimal solutions for small instances, and better near-optimal solutions for larger instances compared with a linear solver, Lingo 8.0, used to solve the equivalent linear integer programming obtained by transforming the original model. Totally, 92.3% of the instances are solved to global optima by the ILS algorithm while it is possible that the other 9.7% instances also are solved to optimal, which indicates the efficiency of the algorithm. At the same time, the algorithm also provides better solutions than the ones obtained by the current system used in the company.


To clarify the interactions between stressful life events and other risk factors in the development of duodenal ulcer disease, we studied 33 patients with active ulcer, symptomatic for ≤ 6 months and untreated during the previous year, using the Paykel Interview for stressful life events, the Minnesota Multiphasic Personality Inventory (MMPI), and Zung's Anxiety and Depression scales. MMPIs were abnormal in 64% of the patients, and 61% showed some degree of depression. The 16 patients whose symptoms had been preceded by severe stress had more pathological MMPIs, especially on paranoia and dependency scales; were more depressed; and had used less nonsteroidal anti-inflammatory drugs than those without p < 0.05). They were somewhat more likely to be single, to be of low social class, and to have recently increased use of cigarettes, alcohol, or coffee (though their absolute level of alcohol consumption was low). Anxiety levels did not differ between stress and nonstress groups. Correspondence analysis yielded four clusters of patients, characterized by (a) alcohol/cigarette use, personality disorder, chronicity; (b) early onset, neurosis; (c) depression, life events; (d) late onset, psychosocial stability. The analysis changed little according to whether life events were or were not considered in cluster formation. We conclude that ulcer patients who become ill under stress form a distinct subgroup, that depressed mood and stress-related increases in use of alcohol and cigarettes may mediate between stress and ulcer formation, and that life events are a quantitatively minor factor in ulcerogenesis.


SUMMARY : The post-transplant lymphoproliferative disorder (PTLD) is defined in large part by their occurrence following organ transplantation and by their histopathological appearance. The vast majority is associated with Epstein -Barr virus (EBV) infection. Their recognition is important because underdiagnosis as a not otherwise specified reactive process may lead to continued immunosuppression and progression of disease and overdiagnosis as a conventional lymphoma may lead to inappropriate and potentially fatal chemotherapy. In this article pathogenesis, clinical cause, and therapy of PTLD have been presented and the role of EBV described.


NMR (600 MHz) studies on YSPTSPSY (1), the heptad repeat unit of RNA polymerase II with an extra tyrosine added to the N-terminus, show that the peptide is partially structured in aqueous solution. Peptide 1 contains two overlapping SPXX sequences and has been reported to bind to DNA by bisintercalation (Suzuki, M. Nature 1990, 344, 562-565). In 90% H2O solution at pH 3.2, the major species, which is present in > 90%, contains Pro3 and Pro6 in the trans conformation. At low temperature (4 degrees C), NOE connectivities are consistent with the presence of beta-turn structures in equilibrium with unfolded forms of the peptide. A strong dNN connectivity between Thr4/Ser5, a d alpha N connectivity between Pro3/Thr4, and a medium-range NOE between Pro3 alpha and Ser5 NH indicate the presence of a beta-turn formed by (i) Ser2-Pro3-Thr4-Ser5. A strong dNN connectivity between Ser7/Tyr8 and weaker dN delta NOE connectivities between Ser2/Pro3 delta and Ser7/Pro6 delta were also detected. The solution conformation of the peptide appears to have a crucial role in determining the interaction of the peptide with DNA, given that only bisintercalation has been reported in DNA-binding studies on 1 (Suzuki, M. Nature 1990, 344, 562-565). On the basis of these results, the peptide unit--SPTSPS--(3) has considerable potential as a structured linker in the preparation of DNA bisintercalators of the general structure Xaa-SPTSPS-Zaa (2) with improved selectivity properties.


In late 2019, SARS-CoV-2 emerged in the Wuhan province of China. Rapid global spread led to the Covid-19 pandemic. Rapid and accurate detection of SARS-CoV-2 has become a vitally important tool in controlling the spread of the virus. Lateral flow devices (LFDs) offer the potential advantage of speed and on-site testing. The sensitivity of these devices compared to the gold standard RT-PCR has been questioned. We compared the performance of the Innova lateral flow kit, recommended by the UK government, with our rapid in-house RT-PCR protocol using stored positive patient samples. The LFD device was found to be 6,000-10,000 times less sensitive than RT-PCR for the detection of SARS-CoV-2. Overall, the LFD detected 46.2% of the positives detected by RT-PCR. 50% of the LFD results were observed to be weak positives, only visible after careful examination by experienced laboratory staff. At lower viral loads, such as 10,000-100,000 RNA copies/ml, the LFD detected 22.2% of positives. In addition, two strong positives (3 and 1.5 million RNA copies/ml) were not detected by the LFD. The argument for use of LFD kits, despite their lack of sensitivity, is that they detect infectious virus and hence contagious individuals. At present, there is a lack of scientific evidence supporting this claim. The LFD used in the UK fails to identify individuals with considerable viral loads and has been subject to a class I recall by the US FDA but is still approved and recommended for use by the UK government. We believe that using LFD testing for assessing SARS-CoV-2 infection risk is a strategy which has risks that outweigh any benefits.


Entrepreneurship is essential to Indonesia's economic development. It is evidenced by 99.9 percent of all Indonesian firms are micro, small, and medium-sized enterprises (MSMEs). Entrepreneurship is regarded as a phenomenon that has received the greatest attention in recent years. Among scholars, there is a strong desire to investigate the entrepreneurial phenomena not only because of its unavoidable importance in boosting the economy and creating job possibilities. Young generations play an essential part in entrepreneurial ventures since they are more likely to start a new business than older generations. However, research studies found Gen Y and Gen Z have different characteristics, which leads to differences in entrepreneurial orientation. The study successfully collected the primary data from 389 newbie entrepreneurs who distributed closed-ended questionnaires using a 5-point Likert scale. This study adds significantly to the existing entrepreneurial literature by examining entrepreneurial orientation between these two generations based on three dimensions: innovativeness, proactiveness, and risk-taking. In addition, the Rasch model was used in this study. The study's outcomes demonstrate a significant difference in risk taking dimension between gen Y and gen Z. Practical implications based on this research of entrepreneurial orientation among the two generations can be empowered through entrepreneurial education programs. The study provides the recommended methods to develop each gen Y and gen Z entrepreneurs.


The article presents a study of the predictors for successful self-disclosure of high school students' abilities in the 11 grade. The main categories of research are presented. We substantiated the problem of the uncertainty for predictors in the context of self-disclosure of the high school students' abilities. The definition of the concept of self-disclosure of abilities is given, which is the result of a dialogue with oneself, due to which high school students understand what abilities are peculiar to them. The success of self-disclosure of abilities reflects the coincidence of abilities, chosen as one's own, and ones, obtained using psychodiagnostic techniques. It is assumed that abilities predetermine a choice of the appropriate type of activity that brings satisfaction, makes it easy to navigate professional activities and succeed in it. The analysis of domestic research studies is presented, within which a methodology for the study of abilities by English-speaking authors is presented, that, despite differences in terminology, discovered a number of interesting facts. The results of an empirical study conducted on a sample of 30 eleventh-graders are shown. The predictors of successful self-disclosure were the reflective components of the personality, the acceptance of oneself, one's personal values, stable inherent worth, responsibility, the kinesthetic type of intelligence, and practical skills. The teacher's assistance, supposedly instructive in nature, prevents the successful self-disclosure of the high school students' abilities.


Abstract Dolerite dyke swarms are widespread within the Singhbhum Craton (eastern India) that emplaced from the Neoarchean to Paleoproterozoic era just after the stabilization of crust before c. 3 Ga. These dyke swarms are oriented in NE–SW to NNE–SSW, NW–SE to WNW–ESE, east–west and north–south directions. The WNW–ESE-trending c. 1.77 Ga Pipilia dyke swarm is sampled from the Satkosia area of Orissa state. The dyke shows a noticeable disparity in terms of the modal proportion and grain size of pyroxenes, plagioclase, Fe–Ti oxide minerals and texture across the trend. In places the primary silicates are altered to secondary hydrated mineral assemblages of amphibole, chlorite and sericite. The primary silicates are clinopyroxene (augite – Mg# = 65.7–82.6; En37–48Fs11–17Wo36–41), orthopyroxene (clinoenstatite – Mg# = 68.5–78; En63–70Fs20–29Wo4–5) and plagioclase (An11–39Ab44–82Or1–7) and the Fe–Ti oxides are titanomagnetite (FeO, 34.38–39.50 wt%; Fe2O3, 48.26–56.21 wt%; TiO2, 5.05–9.60 wt%) and ilmenite (FeO, 40.75–43.79 wt%; Fe2O3, 3.54–10.03 wt%; TiO2, 47.82–50.87 wt%). Application of two-pyroxene thermometry yields an equilibration temperature range of 1065–978°C, and coexisting titanomagnetite–ilmenite pairs reveal 731.39–573.37°C under the oxygen fugacity (fO2) condition NNO + 0.3 to FMQ − 1.03. The dyke contains disseminated sulfides at the interstices of Fe–Ti oxides and silicates. Major sulfide minerals are pyrite, chalcopyrite and vaesite; pyrite–vaesite assemblages occur in association with secondary silicate minerals. Pyrite grains contain variable concentrations of Co (0.01–5.70 wt%) and Ni (0.02–1.95 wt%). Coexisting vaesite contains Co (2.42–10.44 wt%), Ni (26.40–47.88 wt%) and Fe (7.32–26.55 wt%). Texture, sulfide–silicate assemblage and the presence of low metal/S sulfides such as the pyrite–vaesite assemblage indicate that primary Fe–Ni sulfides (pyrrhotite–pentlandite) that segregated from immiscible sulfide liquid at high temperature are modified by late magmatic/hydrothermal fluid activities. Numerous sulfide-bearing deposits hosted in ultramafic–mafic intrusions of Paleoproterozoic age have been recorded globally and the occurrence of Fe–Ni sulfides in the c. 1.77 Ga Pipilia dyke swarm in the Singhbhum Craton enhances the exploration potential of this craton in eastern India.


UNLABELLED
Background Patient information leaflets (PILs) are widely utilised within publically funded sexual health clinics to deliver sexual health-related information (SHRI); however, their continued value to clients in the era of social media is unclear. This study aimed to evaluate clients' opinions on three newly developed PILs and examine client views on other forms of SHRI delivery.

METHODS
An anonymous self-administered questionnaire was completed by clients attending the Western Sydney Sexual Health Centre (WSSHC) in 2012. High-risk population (HRP) vs non-high-risk population (non-HRP) views on PILs vs alternative methods of SHRI delivery were analysed by using Mann-Whitney U, Wilcoxon, McNemar and χ(2) tests.

RESULTS
Over half (210/315; (67%)) of the consecutive clients from a culturally diverse population completed the survey. Sex workers (SW) and young people (YP) were significantly likely to have a high school education than non-HRP (P<0.039 and P<0.032). Overall, PILs, a clinic website and the Sexual Health Information Link (SHIL), a state-wide website and telephone line, were ranked significantly higher as a means of SHRI delivery on a Likert scale than newer technologies including Facebook (P<0.001), email (P<0.001), mobile phone applications (P<0.001), TVs in waiting rooms (P<0.001) and business cards (P<0.001). There was no significant difference in opinion between HRP and non-HRP.

CONCLUSIONS
This study provides evidence for the ongoing use of PILs to deliver SHRI to clinic attendees, in conjunction with other forms of SHRI delivery such as websites and SHIL. Novel methods may require additional consumer engagement and a greater understanding of specific population's needs.


This study was performed to develop a precise single residue analytical method of fungicide cyprodinil in representative crops for using as general residue analytical methods which could be applied to most of crops. Apple, mandarin, Korean cabbage and green pepper were selected as representative crops, and they were macerated, extracted with acetonitrile, concentrated and partitioned with n-hexane. Then the extracts were concentrated and cleaned-up through silica gel column with ethyl acetate:n-hexane (15:85, v/v) before concentration and analysis with HPLC. LOQ (limit of quantitation) of cyprodinil was 5 ng (S/N>10) and MQL (method qnantitation limit) was 0.05 mg/kg. Recoveries were measured at three fortification levels (MQL, 10MQL and 100MQL) on crop samples and ranged from 82.0 to 108.2% and coefficients of variation were less than 10% regardless of sample type.


This study aims to determine: (1) how the assessment discipline of Physical and Health Education's Lesson at State Junior High Shcool 2nd Gombong Kebumen Regency year 2014/2015 teachers do at this point, (2) how the shape of the instrument, (3) how the development of the instrument, (4) what are an indicator instrument, (5) the validity and reliability of the instrument, (6) the tendency of attitude measurement results of discipline, (7) the relationship between Physical and Health Education's Lesson with value discipline, and (8) the difference between the student discipline men with female students. This type of research is the development of research. This research was conducted in SMP Negeri 2 Kebumen Gombong. The subjects were: A seventh-grade students of State Junior High Shcool 2 nd Gombong Kebumen Regency which amounts to 32 students and teachers of State Junior High School 2nd Gombong Kebumen Regency Deal. The object of this study is discipline assessment instruments Physical and Health Education's Lesson. Based on the results of the study concluded: (1) is now part of teacher disciplinary assessment Physical and Health Education's Lesson at Junior High School 2 Gombong by observation alone without the use of assessment instruments, (2) The form of assessment instruments Physical and Health Education's Lesson disciplinary subjects consisted of observation instruments the value of discipline, instruments self-assessment and peer assessment instruments, (3) development of assessment instruments disciplinary subjects between the stages Sport and Healt done, namely: literature study and field surveys, the development of assessment instruments of discipline, expert validation and revision of the product, product trials, data analysis, and the final product, (4) Indicators discipline assessment instruments, namely: (a) the right time on Physical and Health Education's Lesson, (b) comply with the rules or school rules and regulations Physical and Health subjects, (c) do/collect duties in accordance with the time Physical and Health determined, and (d) follow the rules of good writing and speaking correctly, (5) the validity and reliability of the instrument all valid and reliable instruments, (6) the results of measurements of the attitude of discipline at State Junior High Shcool 2nd Gombong Kebumen Regency including good category, and (7) There is a difference between male students with discipline female students in class VII A State Junior High Shcool 2nd Gombong Kebumen Regency Deal.


University language centres provide language-based courses to students
 of all disciplines. The principal raison d'être of a university language
 centre is to support any number of learner types, with a variety of reasons
 for learning a second or foreign language at tertiary level. These may
 include students and staff, external partners, and members of the public as
 part of a wider outreach strategy (Critchley, 2015). Language centres offer
 credit-bearing language courses and language enhancement programmes, general
 education, and service learning subjects. They also offer subjects for
 postgraduate research students and masters programmes. Qualities of
 pedagogic innovation, institutional adaptability, and effective use of
 technology have contributed to language centres' successful development
 (Ruane, 2003). Nonetheless, faculties of language centres offer more than
 their teaching, as many are involved in research activities...


The trade-off between users' fairness and network throughput may be unacceptable in a multi-rate 802.11 WLAN environment. In this paper, we will design a new intuitive simplified mathematical model called simplified coefficient of variation (SCV) to closely reflect our topic. Through controlling the power of Access Points, SCV can optimize and improve the performance. Since our topic is a NP-hard problem, we use Ant Colony Algorithm to solve our model in a practical scenario. The simulation shows excellent results indicating that our model is efficient and superior to an existing method. Also we use software SAS to further reveal the relationships among the three indicators to illustrate the essence of our approach and an existing algorithm.


The aim of this study is to develop a lesson plan for the "Graphics and Animation in Education" course lectured in the department of Computer Education and Instructional Technology (CEIT). For this purpose, a "Needs Analysis Form for Graphics and Animation in Education Course" that includes open ended questions is produced by the program specialist and the researchers. The needs analysis form was applied to 10 instructors who have taught this course in the faculty of education. In the light of the findings derived from the needs analysis; the purpose of graphics and animation in education course was determined as: "creating e-materials which specifically comprise interactive features in order to use at various levels of education and providing students the skills to adapt these materials to be used in mobile devices". The basic strategy to use for this course is stated as "Expository" and during the course demonstration and question-and-answer methods are used. As a result, a lesson plan was developed for a unit of the graphics and animation in education course.


Property valuers, first of all, asses the value of the rights to the property. The enterprise, itself, is not that often the subject of their valuation. In case of enterprises carrying out its business activity at the special purpose property, the proper definition of the valuation subject (is it an enterprise or a property?) and the selection of the valuation method constitute a key issue.The valuation of the commercial property generating income in relation with the business activity carried out there, such as for example a fuel station, is done using the profits method basing among others on historical sale and cost data. The profits method requires both the knowledge of the market specificity where a given valuated property operates and of the trade executed by a reasonably efficient operator (REO) there. Obtaining the income from this type of property is conditioned by having current assets (e.g. fuel and nonfuel goods in case of fuel stations), equipment, employees, etc. It results in numerous similarities in the calculation of the net operating income for property valuation to the calculation used to assess the enterprise value with a discount cash flow (DCF) method. However, there are many differences with regards to this calculation which do not let equate the property valuation calculation with the valuation of the enterprise carrying out its activities at the special purpose property such as a fuel station.The presentation focuses on the comparison analysis of the calculation of the special purpose property market value in profits method and the calculation of the fuel station valuation as an enterprise in DCF method. The comparison analysis of fuel station valuation also shows both the similarities and differences between the valuation based on the Polish standards and the RICS (Royal Institution of Chartered Surveyors) standards. The aim of the research is to show the differences between the valuation of the fuel station as a property using a profits method and the valuation of the fuel station as an enterprise using a DCF method. Literature studies and case studies were used in the research. The research was carried out from November 2016 to February 2017.


The New Zealand Thoroughbred industry has seen rationalisation in response to changes in the domestic market and more recently the Global Financial Crisis (GFC). To quantify changes in production, end-of-season reproductive data for active Thoroughbred sires were extracted for the 1989/90 to 2011/12 breeding seasons. There were reductions in the numbers of mares bred and foals produced (10,176 mares & 5,882 foals vs. 5,826 mares & 3,927 foals, respectively in 1989/90 and 2011/12 seasons) resulting in a greater relative proportion of foals registrations (57% vs. 67%). During this period, the number of active sires decreased (265 vs. 94) and number of mares per sire increased (33 IQR 18-53 vs. 49 29-91). The 2007/08 season (GFC) was associated with an acute reduction in the number of shuttle stallions imported for breeding (from 23% in 2006/07 to 11% of active sires in 2007/08), and a temporary increase in number of mares bred (13%), in response to the 2007 Equine Influenza outbreak in Australia. The proportion of sires covering >100 mares per season increased from 6% (1989/90) to 25% (2011/12). Despite the reduction in active broodmares during the same period (43%), there has not been a proportional decrease in export numbers (24%) or domestic numbers of horses racing (6.5%). Introduction In contrast to the majority of the top 10 nations involved in Thoroughbred racing and breeding, the New Zealand industry is heavily reliant on the export market, rather than production of horses as domestic racing product (Fennessy 2010). Previous examination of the production process has identified that approximately 40% of the annual foal crop are exported (Bolwell et al. 2014), and that the industry could be considered to operate as two sectors or tiers – one sector focused largely on the export market and another group of smaller breeders (fewer mares per breeder) focusing on the domestic market (Rogers & Gee 2011). The export market was characterised by the use of shuttle sires (stallions breeding in the Northern and Southern Hemispheres in one calendar year) and expensive sires (>$10,000 service fee), while the domestic market was serviced by the low-cost (<$5,000 service fee) and to a lesser extent, medium-cost sires ($5,000 – $10,000 service fee). While the majority of sires at stud (~70%) could be identified as servicing the domestic market, each of these sires typically sired fewer mares than those used for the export market and, thus, the distribution of mares mated to supply the domestic market accounted for 55% of the annual mating returns (Rogers & Gee 2011). The seasonal and lifetime reproductive efficiency of the Thoroughbred mare is limited by a number of industry practices including the restriction on the use of artificial insemination (AI) and the imposition of a short commercial breeding season. The effective breeding season in New Zealand is 1 September to 30 November, which does not mirror the physiologic breeding season, and this is driven by the perceived need to have foals born as early in the season as possible so they are larger when sold as yearlings and can, thus, maximise sales price (Waldron et al. 2011;Hanlon et al. 2012). The combination of short breeding season and the inability to use AI means a short intense mating period for the sire and most mares are covered (mated) only once per cycle. (Hanlon et al. 2012). In contrast to sport horses, the Thoroughbred industry has a shorter generation interval, as sires are recruited to the breeding ranks shortly after their "classic year" as a three year old which is earlier than the timeframe to provide a competition proof on a sport horse (typically when 8-9 years old) (George et al. 2013). Also contributing to the lower generation interval is the short commercial life of a sire (4 years according to taxation law) and a high replacement rate. It is estimated that only 5% of sires prove themselves as a commercial success and previous analysis indicates that the median career is actually only three years at stud (Rogers et al. 2009). The generation interval on the mare side is also short compared to sport horses, with most mares recruited to stud as six year olds, and then achieving zero book value by the time they are 12 years old (Rogers et al. 2009; Aurich & Aurich 2006). A greater percentage of the mares sired by expensive sires and shuttle sires are recruited into the breeding herd and the median age of recruitment to breeding is 1-2 years earlier than mares sired by the medianand lower-service-fee sires. This industry structure effectively means that the two sectors of the Thoroughbred industry run in parallel with some overlap. In an animal production context (i.e., sheep or beef) the export sector could be considered as the equivalent to the stud stock industry and the domestic sector as analogous to the commercial farmer. In response to changes in domestic demand there has been significant rationalisation within the New Zealand Proceedings of the New Zealand Society of Animal Production 2016. Vol 76: 146-150 147 Thoroughbred breeding industry. This has been reflected in increased industry efficiency with a greater proportion of foals being generated from fewer mares and sires (Rogers et al. 2009). Internationally the 2008 Global Financial Crisis (CFC) was associated with severe contraction in the number of horses breed and racing (Leadon et al. 2012). To date the effect of this on the horse population or number of horses breed has not been investigated. A confounding factor influencing horse production at this time was the 2007 Australian Equine Influenza (EI) outbreak. Australia has historically been numerically and financially the major export market for the New Zealand Thoroughbred, and changes in Australia, or changes in demand, influence New Zealand horse production. The objective of this paper is to describe the changes in New Zealand Thoroughbred production since the last review of breeding efficiency, and describe the impact the GFC and the Australian EI outbreak on New Zealand Thoroughbred horse production Materials and methods Breeding records for all active sires (stallions covering > 10 mares in a breeding season) from the 1989/90 to 2011/2012 breeding seasons were downloaded from the New Zealand Thoroughbred racing website (www. nzracing.co.nz) and imported into MS Excel (Microsoft Corporation, Redmond, WA, USA). The service fee of the sire, age when first standing at stud and number of years at stud were obtained from the sires details listed in the respective Register of Thoroughbred stallions of New Zealand (NZ Thoroughbred Breeders Association (Inc)) for each breeding season. The full breeding records of the active sires permitted calculation of industry data on fertility, foaling percentage, length of breeding season and the age profile of the active broodmare herd. To examine the association of service fee on stallion age, and age of the mares covered the sires were classified as low cost ($2,000-5,000), medium ($5,500-10,000) or expensive ($10,001-100,000). Due to the dramatic reduction in the number of shuttle sires utilised post GFC the category shuttle sires was not used for analysis. Commercial career To estimate the proportion of commercial sires and number of seasons when commercially active (covering ≥50 mares per season) all sires active in 2005/2006 breeding season were categorised as commercial (≥50 mares per season ) or non-commercial (≤ 50 mares per season) in that season of interest. Full breeding records were then extracted and the number of seasons at stud during their career in which the sires could be classified as commercial (≥50 mares per season) were recorded. Data on the period from season of initiation of breeding career until the season of the first non-service period were calculated from data based on the breeding records of all mares that were breed in the 2005/06 breeding season. Statistical analysis Data were examined graphically for distribution and errors in data transcription. After testing for normality, parametric data were examined using a general linear model and presented as mean and standard error. Nonparametric data were tested using a Kruskal Wallis test and presented as median and interquartile range (IQR). For all analysis the data were tested using STATA 12 (StataCorp, TX, USA) using a significance level of P<0.05


This paper presents a coupled design analysis for a Pipe-in-Pipe (PIP) Steel Catenary Riser (SCR) and Flowline (FL) system in 5000ft of water under high pressure and high temperature (HP/HT) conditions in the Gulf of Mexico (GOM).The finite element program ABAQUS is used to model the inner and outer pipes of the PIP system, the centralizer, the SCR hangoff, the flowline lateral and end supports, and pipe-soil interactions on the seabed. Thermal stresses and stress ranges caused by repeated temperature transients, axial and lateral displacements of SCR and flowline, as well as by the dynamic responses of the coupled riser and flowline system, are presented. Comparisons are also made with results by ABAQUS models with beam and pipe elements, and results obtained by coupled and de-coupled analysis. The sample vessel motion was obtained for an example Spar platform in GOM.Copyright © 2014 by ASME


An intelligent interface cannot just respond passively to its user's commands and queries. It must be able to take the initiative in order to volunteer information, correct user misconceptions, or reject unethical user requests. To do these things, a system must be an intelligent agent. UCEgo is the intelligent agent component of UC (UNIX Consultant), a natural-language system that helps the user solve problems in using the UNIX operating system. UCEgo provides UC with its own goals and plans. By adopting different goals in different situations, UCEgo creates and executes different plans, enabling it to interact intelligently with the user. UCEgo adopts goals from its themes, adopts subgoals during planning, and adopts metagoals for dealing with goal interactions. It also adopts goals when it notices that the user either lacks necessary knowledge or has incorrect beliefs. In these cases, UCEgo plans to volunteer information or correct the user's misconception, as appropriate. This is a reprint of chapter 9 in Joseph W. Sullivan and Sherman W. Tyler (Eds.), Intelligent User Interfaces, Addison-Wesley, Reading, MA, 1991, pp. 127–206. This research was supported in part by the Office of Naval Research, under grant N0014-48-C-0732; the Defense Advanced Research Projects Agency (DoD), under Darpa Order No. 4871, monitored by Space and Naval Warfare Systems Command under Contract N00039-84-C-0089; the National Science Foundation under grant #85-14890; and Hughes Aircraft grant #442427-59868.


The need for a physical method by means of which it would be possible to recognise a chemical individual of the protein group of compounds has undoubtedly been one of the factors contributing to the difficulty of research into the chemistry of the proteins. The present methods of chemical analysis do not nearly approach sufficient accuracy to distinguish between successive recrystallisations of a protein substance. The first serious effort to prove that an individual protein could be isolated is to be found in the publication of Hopkins (1900). It was here shown that a protein could be prepared with a constant specific rotation for successive recrystallisations and for material obtained from different sources. Unfortunately, this desirable physical constant, which is independent of the degree of colloidal dispersion, has been shown to vary with variations in physical and chemical conditions. Thus Alexander (1896) found the specific rotation of certain globulins varied according to the concentration of the protein and of salt present. An investigation of this phenomenon by Pauli, Samec and Strausz (1914) confirmed the observations of Hopkins (1900) and of Osborne (1899) that the presence of neutral salts has no influence on the optical rotation of a protein. The addition of acids and of alkalies they found to increase the rotation of polarised light, while the degree of change depended upon the nature of the anion in the case of an acid and of the kation in the case of a base. These observations were made, unfortunately, with the mixture of proteins contained in ox or horse serum which had simply been dialysed until salt-free. The nature of these changes may find explanation in a tautomeric rquilibrium of the lactam-lactim type in the protein main chain when in aqueous solution, as suggested by Robertson (1912) and Sorensen (1912), and to which view Pauli inclines. R—CO—NH—R ⇌ R—C(OH) = N—R. Lactam formula Lactim formula.


Space charge accumulation within polymeric materials has been associated with their accelerated ageing. The measurement of this phenomenon can be used to correlate space charge profiles and their evolution to ageing. In this paper, accumulated charge depletion after long electrical ageing processes has been analyzed following a research trend pointed out in previous works. In order to extend this analysis to several materials, the electrically barely known UHMWPE (Ultra-high molecular-weight polyethylene), mostly used in medical applications, has been compared to well-known XLPE and LDPE. It has been proposed some extremely simple indicators that can be used to know the ageing of a polymeric insulation without incurring in simplifying assumptions and using only the charge profiles obtained directly from the space charge measurements taken by PEA (Pulse Electro Acoustic) method.


Many dynamic reconfigurable processors are evolving rapidly that offer fast and run-time reconfiguration. To efficiently utilize run-time reconfiguration, we must consider additional memory access cycles due to reconfiguration. In general, dynamic reconfigurable processors read input data from external memory after reconfiguration and write output data to external memory before the next reconfiguration. To realize high performance, we must schedule tasks considering the total execution cycles that include reconfiguration time and memory access overhead. In this paper, we propose a parameterized reconfigurable processor model (PRP-model) and a task partitioning optimization algorithm for the architecture exploration of multicontext dynamic reconfigurable processors. The proposed task partitioning algorithm corresponds to various dynamic reconfigurable architectures by changing parameters and can realize the evaluation of a lot of reconfigurable architectures. Experimental results showed that the proposed algorithm can quickly find near optimal solutions. Using the proposed algorithm, designers can easily evaluate the performance of various dynamic reconfigurable architectures for specific applications


Abstract The Swiss Confederation is known for its historical multilingualism. The four national languages are, however, unequally distributed among its inhabitants. Individual foreign-language competence, including English, also varies strongly. The educational system reflects cantonal differences. The article distinguishes between strong, intermediate, and weak forms of trilingual education. The strong form can be found at university level, the intermediate form includes all bilingual models with a course in one additional language, and the weak form is found frequently, in particular, in secondary education. A new model of multilingualism emerges with two national languages, plus English. Research has thus far dealt mainly with the outcomes of bilingual education, but in the near future will focus more on the differences between second- and third-language learning and the outcomes of trilingual education.


This paper is an attempt to share with the reader the experience of being in an immersion in English that helped me to improve my fluency and to understand that teaching English with the purpose of communicating would help our students, our schoolsand the standards of quality in Colombia. The program is then an excellent strategy to qualify English language teaching and has been very appropriate for the particular situation of our country.


We have found that type II topoisomerase inhibitors have two effects on replicating simian virus 40 genomes in vivo: production of catenated dimers and slowed replication of the last 5% of the genome. This suggests that type II topoisomerase simultaneously decatenates and facilitates replication fork movement at this stage of DNA replication. On the basis of this observation, a detailed model is proposed for the roles of topoisomerases I and II in simian virus 40 DNA replication.


Abstract Based on research undertaken as part of the EU funded EPPIC project, this paper aims to update and elaborate on the relationship between drug use and offending behaviours by exploring variations within a cross-national sample of drug-experienced young people in touch with criminal justice systems. Adopting a trajectory-based approach, interviews were undertaken with 198 young people aged 15–25 in six European countries (Austria, Denmark, Germany, Italy, Poland, and UK). Data were analysed by applying the Bennett and Holloway categorization of the drugs-crime link, with a focus on the concept of social exclusion as developed by Seddon. Three main types of mechanisms (economic, pharmaceutical, and lifestyles) are used to interpret the data, showing how the relationship between drugs and offending can vary according to type of substances and over time. Furthermore, it can be associated with very different degrees of social exclusion and needs. The results suggest that while economic inequalities still play key roles in explaining drug use and offending, both behaviours can originate from a state of relative deprivation, resulting from the contradictions inherent in 'bulimic societies' that raise aspirations and desires while providing young people scarce opportunities for self-realisation and social recognition.


ABSTRACTMany applications of the Inverse Gaussian distribution, including numerous reliability and life testing results are presented in statistical literature. The paper studies the problem of using entropy tests to examine the goodness of fit of an Inverse Gaussian distribution with unknown parameters. Some entropy tests based on different entropy estimates are proposed. Critical values of the test statistics for various sample sizes are obtained by Monte Carlo simulations. Type I error of the tests is investigated and then power values of the tests are compared with the competing tests against various alternatives. Finally, recommendations for the application of the tests in practice are presented.


We consider simulation optimization under input uncertainty, where the unknown input parameter is estimated from streaming data arriving in batches over time. Moreover, data may depend on the decision of the time when they are generated. We take an online approach to jointly estimate the input parameter via Bayesian posterior distribution and update the decision by applying stochastic gradient descent (SGD) on the Bayesian average of the objective function. We show the convergence of our approach. In particular, our consistency result of Bayesian posterior distribution with decision-dependent data might be of independent interest to Bayesian estimation. We demonstrate the empirical performance of our approach on a simple numerical example.


With the aid of symbolic computation system Maple, many exact solutions for the (3+1)-dimensional KP equation are constructed by introducing an auxiliary equation and using its new Jacobi elliptic function solutions, where the new solutions are also constructed. When the modulus m → 1 and m → 0, these solutions reduce to the corresponding solitary evolution solutions and trigonometric function solutions.


Much of the public was introduced to the implantable cardioverter-defibrillator (ICD) when Vice President Cheney, a survivor of four heart attacks, received the device in 2001. Although ICDs were initially limited to patients with previous cardiac arrests or arrhythmias, more recent studies have demonstrated that ICDs can prevent sudden cardiac death in patients who have not had a cardiac arrest, but are at greater risk for one (for example, those with congestive heart failure and reduced cardiac function). This Issue Brief summarizes studies that analyze health outcomes, costs, and quality of life for patients-at-risk who receive ICDs in real-life settings.


In recent Western and Chinese scholarship on discourses of ethnicity in south-west China, there has been an emergent interest in the mechanism of memory and forgetting in relation to formations of ethnicities and frontier space. In Southwest China, perhaps no figure has been more important than Zhuge Liang, a famous strategist during the Three Kingdom Period (220–280 AD), whose Nanzheng (Southern Expeditions) military operation left many legends among ethnic minorities in the region, often associated with the origins of a multiplicity of place names and cultural attributes. However, in the melodrama of ethnic unity after 1949, Zhuge Liang has been championed as a benevolent figure whose ethnic policy successfully transformed the historically volatile southwestern minority regions and brought them into the fold of the Chinese nation. Based on archives and oral interviews, this paper examines the twists and turns in official and indigenous interpretations of Zhuge Liang's legacies in southwest China. It analyses oral traditions of Zhuge Liang in the Tibetan border city of Kangding as well as in Yi and Han places. The paper intends to highlight individual and specific aspects related to the construction of frontier space and memory in conjunction with the negotiation and contestation of visions of local and official histories.


Following a previous experiment, this paper presents our ongoing effort to improve a rapid multisensory non-individual HRTF adaptation training method. Motivations to modify our former attempt of an audio-visuo-proprioceptive training are first presented. The paper mainly focuses on two aspects: the inclusion of a non-individual HRTF pre-selection phase, and the design of relevant visual cues, consistent with the auditory cues. The design of an experiment, planned to investigate the effect of vision on the adaptation to non-individual HRTF, is then detailed. We conclude with some expected results and future research directions and a new context of use: the rehabilitation of patients suffering from spatial cognition disorders.


This essay seeks to reconsider the relation of the universal-rational ethos of Spinoza's thought to the Jewish tradition and culture in which he was raised and socially situated. In particular, I seek to engage with two previous portrayals—specifically, those of Isaac Deutscher and Yirmiyahu Yovel—that present Spinoza's universalism as arising from his break from or transcendence of Judaism, where the latter is cast primarily (along with Christianity) as a historical-particular and therefore non-universal tradition. In seeking a potential source of Spinoza's orientation, Yovel points Marrano culture, as a sub-group that was already alienated from both mainstream Judaism and mainstream Christianity. By contrast, I argue that there are key elements of pre-Spinoza Jewish-rabbinic conceptuality and material culture that already enact a profoundly universalist ethos, specifically in contrast to more parochialist or particularist ethical dynamics prevalent in the culture of Christendom at the time. We will see, furthermore, that the Marrano dynamics that Yovel fruitfully highlights in fact have much in common with dynamics that were already in place in non-Marrano Jewish tradition and culture. As such, we will see that Spinoza's thought can be understood not only as manifesting a Marrano-like dynamic in the context of rational-philosophical discourse, but also as preserving a not dissimilar Jewish-rabbinic dynamic at the same time. This, in turn, will point to new possibilities for tracing this latter dynamic through the subsequent history of modern philosophy and modern Jewish thought.


The seismicity of the Monterey Bay displays a sparse distribution of events with a majority in northern Monterey Bay, on the San Gregorio fault. The paucity of near-shore and offshore seismic recording instruments and the use of velocity models from inland regions for earthquake hypocentral locations and focal mechanisms have led to uncertainties and inaccuracies for seismic events on major faults that crosscut the Bay. New three-component seismic data were acquired during 1997–1999 by the Monterey Bay Aquarium Research Institute (MBARI) Margin Seismology project using ocean-bottom digital corehole and standard seismometers, and coastal digital RefTek instruments obtained from IRIS-PASSCAL by the University of California, Santa Cruz. We have analyzed phases from earthquakes in the Monterey Bay vicinity located by these instruments and used them to supplement the adjacent coastal stations of the permanent Northern California Seismic Network. A new one-dimensional velocity model for the region requires slow velocities from 2 to 6 km that we attribute to sheared granites observed in the Salinian Block in the center of Monterey Bay. Velocities in the 10–16 km layer are consistent with continental crustal velocities. A sharp increase in velocity at ∼16 km suggests a boundary that results from underplating of oceanic crust. This underplated zone appears to extend to a depth of ∼27–30 km where we observe normal upper mantle velocities near 8.0 km/sec. New details from the ocean-bottom corehole and coastal RefTek instruments for events along the SGF and Monterey Bay fault zones hint at local fine-scale structures and have implications for tectonic history and plate reconstruction interpretation.


The antigen-binding capacity of the peptide chains of horse anti-(diphtheria toxin) has been studied by using (125)I-labelled toxoid and electrophoresis of antibody-antigen mixtures on cellulose acetate. The heavy chains retained about 20% of the activity of the whole antibody and the light chains less than 5%. Recombination of specific heavy and light chains gave about 60% recovery of activity and recombination of specific heavy chains and non-specific light chains about 40% recovery. It is suggested that these results favour the heavy chain as the major site of the antigen-binding activity.


Text interpretation often requires common sense knowledge and reasoning. A convenient tool for developing methods of common sense reasoning are special sets of challenge problems whose interpretation requires sophisticated reasoning. An interesting example is a recently published data set called Triangle Choice of Plausible Alternatives (Triangle-COPA), which contains 100 multiple-choice problems that test the interpretation of social scenarios. Each problem includes a statement and two alternatives. The task is to identify the more plausible alternative. For processing Triangle-COPA data we use SemETAP, a general purpose semantic analyzer. We implement the full scenario of NL understanding starting from NL texts and not from manually composed simplified logical formulas, which is a common practice in logic-based approaches to common sense reasoning. We produce Enhanced Semantic Structures of the statement and both alternatives and check which alternative manifests more semantic agreement with the statement in terms of inferences.


Purpose
Communication is crucial for patient experience and biomedical outcomes. Training programs improve communication but are too resource-intensive for sustained use across an entire health care organization. This study demonstrates in a heterogeneous set of encounters the efficacy of quantitative feedback on two groups of physician communication behaviors: 1) jargon explanation, and 2) assessment of patient understanding.

Methods
We used a secure Internet application to audio-record conversations between primary care physicians and 54 patients. Transcripts were quantitatively abstracted using explicit-criteria definitions for assessments of understanding and jargon explanations. These data were conveyed to physicians using a previously tested report card. Finally, physicians were audio-recorded with 48 other patients and compared against their baseline.

Results
Baseline transcripts included an average of 15.5 unique jargon words. Many words were spoken more than once so the total jargon count averaged 25.1. Jargon explanations were infrequent (median of 2.6/transcript). The jargon explanation ratio (fraction of jargon words spoken after or alongside a jargon explanation for that word) averaged 0.26 out of 1.0. Assessments of understanding were found in 61.1% of transcripts, but most were "OK?" questions (median of 2.22/transcript) or close-ended assessments of understanding (median of 0.59/transcript). After the report card, use of jargon explanations improved to a median of 4.8/transcript (P<0.001), and the jargon explanation ratio improved to 0.37 (P<0.02). Assessments of understanding improved to 81.3% of transcripts (P<0.03), largely due to increased use of close-ended assessments of understanding to 1.08/transcript (P<0.006).

Conclusions
It is feasible to audio-record at the point of care, abstract transcripts at a central office and improve physician-to-patient communication quality via a report card. A larger, multifaceted program may improve patient experience and biomedical outcomes.


Purpose of review This review provides an overview of reconstructive robotic procedures in urology. Recently, robotic surgeons have described techniques in urologic reconstruction. We summarize the literature regarding outcomes and surgical steps for robotic pyeloplasty, robotic ureteral neocystostomy with ureteral reimplantation and robotic ureteroureterostomy/ureterolithotomy. Recent findings Outcomes reveal robotic assistance has greatly decreased the morbidity of urinary tract reconstruction, when compared with open surgical techniques. In addition, the superior visual and manual acuity of the robot allows one to perform surgical steps easier as compared with conventional laparoscopy. Summary Robotic assistance provides many benefits for urinary tract reconstruction and in this review we outline the salient features, with the goal of adding these techniques to the urology armamentarium. Future outcome studies need to confirm the long-term efficacy of these techniques.


Here we describe a reliable method for purifying large amounts of RNA of any sequence and length with comparable efficiency and resolution of gel electrophoresis and with capacity approaching that of column chromatography. The RNA mixture of interest is separated on a cylindrical denaturing polyacrylamide gel, eluted by a peristaltic pump, detected by a UV-vis detector, and collected by a fraction collector. Using this method, we were able to separate one third of a 100 ml in vitro transcribed 34mer hammerhead ribozyme (approximately 6.2 mg) in a single run. The entire 100 ml transcribed RNA (approximately 18.5 mg) was separated after consecutive runs using one single gel preparation.


This paper studies localization effects of knowledge spillovers in Korea using US patents granted over the period 1996-2015. The i°sample-matchingi± analysis initiated by Jaffe, Trajtenberg, and Henderson(1993) is adopted. We do not find evidence of positive localization effects in Korea. In particular, controlling for the existing geographic distribution of knowledge production, the frequency of domestic citations of Korean patents is no more than the citation frequency from overseas. We also examine localization effects across regions and industries. Our findings suggest a potential role for government policy aimed at promotion of positive innovation externalities within the Korean economy.


The complex composition of petroleum and the chromatographic challenge it presents has led to its study becoming a key field in contemporary scientific research. Rising concerns over the impact of petroleum within the environment have spurred the need to fingerprint and identify individual oils in order to understand its fate within the environment. The complexity of petroleum lies solely in its origins and thermal processes it undergoes during formation, resulting in it containing hundreds of thousands of different, unknown organic compounds. The majority of petroleum is observed in GC analysis as a 'hump' of unresolvable peaks; this characteristic hump is known as the Unresolved Complex Mixture or UCM. There have been several advances in the separation of oil e.g. GC×GC-MS, dedicated to resolving and identifying compounds within the UCM that could be potential toxicological hazards within the environment. This has led to the unique method of synthesising model UCMs and the possible compounds believed to be within petroleum. Previous investigations, involving the synthesis of C 19 T-branch alkanes have provided evidence to suggest that such structures are present within the aliphatic fraction of some UCMs. This has led onto the synthesis of C 19 H-branch alkanes for the purpose of identifying them within the aliphatic UCM and studying the chromatographic effect of branching within alkanes. A C 19 H-branch alkane was successfully synthesised following the improvement of a Grignard reaction, producing a 3° alcohol which was subsequently dehydrated and hydrogenated to give the desired 5,7-substituted alkane. Comprehensive analysis was performed throughout the investigation, utilising FT-IR, GC-FID and GC-MS, to identify the products of the reactions and confirm the final structure of the desired H-branch alkane. The retention index for the completed H-branch subdivision was calculated and compared with previously studied H- and T-branch alkanes along with pristane; prior to this investigation commonly known to be the earliest eluting C 19 alkane. As a result of this study, two of the H-branch alkanes are now known to have retention indices of 1688 and 1692 Kovats, being lower than n-heptadecane and pristane at 1707 Kovats, making them some of the earliest eluting C 19 branched alkanes.


Room temperature ionic liquids (IL) and deep eutectic solvents (DES) are known to aid the conformational stability and activity of proteins and enzymes in aqueous solutions. They are popular alternatives to harsh organic protecting osmolytes offsetting the thermal/chemical denaturation of proteins due to their greener attributes and low costs. In this paper, using extensive molecular dynamics (MD) simulations we show that a small helix–rich protein, chicken villin headpiece subdomain (HP-36), is rendered stable by an IL, triethylammonium acetate (TEAA) in aqueous solutions containing very high concentrations of urea (8 M). For comparison, the protein is also simulated in a deep eutectic mixture composed of 4 M choline chloride (ChCl) and 8 M urea under identical simulation conditions. Our simulations clearly show that a sharp increase in the relative proportion of TEAA (from 1 : 5 to 1 : 2 with respect to the denaturant urea) does not have a pronounced structure-enhancing effect on the protein. In contrast, for ChCl to function as an efficient protein stabilizer against the harsh action of urea, deep eutectic conditions are mandatory. To the best of our knowledge, this is the first study investigating the comparative aspects of the microscopic properties of a protein in an IL and a DES having similar ammonium-based structural frameworks.


Multiple myeloma (MM) is molecularly heterogenous disease with significant genomic instability. It carries number of mutations at diagnosis (median > 7000) and acquires additional changes overtime. With this background, we have evaluated the molecular intermediates of genomic instability in MM. Based on our large transcriptomic data we have identified apurinic/apyrimidinic deoxyribonuclease (APEX) as an important target whose elevated activity contributes to dysregulation of homologous recombination (HR) and genome stability in MM. Our investigation also demonstrates that transgenic overexpression of APEX nucleases induces genomic instability, leading to oncogenic transformation and tumorigenesis in a murine and Zebrafish models. Importantly, we have now observed that both transgenic as well as chemical inhibition of APEX1, reduces DNA breaks, HR activity and genomic instability as measured by micronucleus assay, and induces G2/M arrest in myeloma as well as esophageal cancer cells.
 To identify novel and effective inhibitors of APEX1, we optimized a high throughput APEX1 activity assay and screened a custom library of 100,000 small molecules. We identified API-93 as an effective APEX inhibitor in both the primary and secondary screens, and have now investigated it, alone as well as in combination, with existing myeloma drugs, for impact on different parameters of growth and genome maintenance. Although API-93 had minimal single agent cytotoxic effect on MM cells, it synergistically increased cytotoxicity of chemotherapeutic agent cyclophosphamide in both MM cell lines (MM1S and RPMI) tested, and also increased the efficacy of melphalan in several MM cell lines (RPMI, MM1R, KK1 and LR5) tested. A strong synergistic effect of API-93 was also observed in combination with lenalidomide in 5 MM cell lines tested (RPMI, MM1S, MM1R, KK1, H929; combination indexes < 1) as well as velcade in MM cells.
 For evaluation of impact on genomic changes, myeloma cells were treated with API-93, live cells purified and evaluated for impact on DNA breaks (by measuring levels of γ-H2AX), DNA end resection (a decisive step in the initiation of HR, by monitoring levels of p-RPA32), and genome stability by investigating micronuclei (the marker of genomic instability). Treatment with API-93 reduced spontaneous as well as melphalan-induced DNA breaks, DNA end resection as well as genomic instability (as assessed by significant reduction in micronuclei) in MM cells, in a dose-dependent manner. To further confirm the impact on genome stability, the MM cells were cultured in the presence or absence of API-93, and the acquisition of new copy number changes over 3 weeks were measured using SNP arrays, in the cultured relative to Day 0 cells (representing baseline genome). Relative to control cells, the cells treated with API-93 resulted in dose-dependent decrease in the acquisition of new copy number events, from 50% to > 90%.
 In conclusion, these data demonstrate APEX gene as being associated with MM cell survival and with genome instability. The novel APEX1 inhibitor, identified in a functional screen, provides an important tool to augment cytotoxicity of the current therapeutics while significantly decreasing genomic evolution in MM.

 Munshi: Adaptive: Consultancy; Takeda: Consultancy; Amgen: Consultancy; Legend: Consultancy; Janssen: Consultancy; C4: Current equity holder in private company; OncoPep: Consultancy, Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties; BMS: Consultancy; AbbVie: Consultancy; Karyopharm: Consultancy.


10 good dream recallers spent 2 nights in the sleep lab during which they were awakened 4 times per night from REM sleep, twice during their highest alpha activity in REM, and twice during low REM alpha. 5 were given alpha feedback training prior to sleep onset. Arousals from high alpha REM sleep yielded significantly higher lucidity ratings. Alpha feedback had no effect upon lucidity or REM alpha levels. Similarities between lucid dreams and meditative phenomena are discussed.