This paper describes a valid and reliable method to com- pare salivary xylitol concentrations during use of xylitol- containing products using a standardized and powerful method of chemical analysis, high performance liquid chromatography (HPLC). HPLC is a method of separat- ing, identifying, and quantifying compounds in a sample. It has been used previously to measure xylitol and other sugar alcohols in gum and confectionary products [12,13]. For the HPLC assay, the lower limit of detection of xylitol, using the standard curve, is 0.2 ng/mL. Validity is the extent to which a test accurately measures the desired phenomenon it is attempting to measure . Reliability is the extent to which the test is in agreement, where agreement may occur across two time periods (e.g., test-retest), between comparable forms of the same test, between individual sections of a test, or among different raters [15-17]. Two studies which address the presence and time course of xylitol in saliva delivered via a variety of xylitol-containing products are described. This paper specifically examines the presence and time course (peak and duration of detectable amounts) of xylitol concentra- tions in saliva for xylitol chewing gum (pellet and stick forms), xylitol gummy bear, and xylitol syrup; and com- pares the total xylitol-saliva time course curve (area under the curve) of xylitol pellet chewing gum to a commercially available xylitol stick gum, xylitol gummy bear and xylitol syrup.
Indeed, at low excitation energies the decay probability strongly depends on J . Therefore, important deviations between the neutron-induced results and the ones obtained with the surrogate method may exist if the populated spin distribution in the neutron-induced and surrogate experiments are different. While it is rather well established that the surrogate method works well for fission at sufficiently high E ∗ (see e.g. ), several recent experiments have shown that gamma decay is very sensitive to the differences in the populated J distributions ([3–5]), which leads to important discrepancies between the surrogate results and the neutron-induced data at low excitation energies. This is probably due to the spin-parity selectivity of neutron emission . This selectivity decreases strongly as the level density of the residual nucleus after neutron emission increases. Therefore, the discrepancies between the surrogate results and the neutron-induced data are expected to decrease with increasing mass of the decaying nucleus and with increasing excitation energy. In this work we study the validity of the surrogate method in the actinide region using an improved experimental set-up that enables the measurement of fission and gamma-decay probabilities. Thanks to this we can investigate the two main issues that determine the validity of the surrogate method: the “compound” character of the decaying nucleus and the J dependence of the decay probabilities.
populated in the neutron and transfer reactions. Therefore, considerable deviations between the neutron-induced results and the ones obtained with the surrogate method may exist. While it is rather well established that the surrogate method works well for fission at sufficiently high E* (see e.g. ), several recent experiments have shown that gamma decay is very sensitive to the differences in the populated J π distributions [3-5], which leads to significant discrepancies between the surrogate
reactions considered in  the excitation energy of the decaying nuclei was high enough for the Weisskopf- Ewing approximation to be valid. In radiative capture reactions, however, we have to consider the competition with neutron emission to the ground or first excited states which is much more sensitive to the differences between the spin-parity distributions . In addition, in the case of actinides, one may need to distinguish between gamma rays originating from the fission fragments and radiative capture gamma rays. This can make radiative capture measurements extremely complicated. Therefore, as a first step we have chosen to investigate the validity of the surrogate method for radiative capture reactions on rare earth nuclei. In particular, our aim is to study the transfer reactions 174 Yb ( 3 He,pγ) 176 Lu and 174 Yb ( 3 He, 4 Heγ) 173 Yb
In Ref.  we showed that our results for the fission cross sections obtained with the surrogate method are in very good agreement with the neutron-induced data at low excitation energies. The reason is that for all the reactions considered in  the excitation energy of the decaying nuclei was high enough for the Weisskopf-Ewing approximation to be valid. In radiative capture reactions, however, we have to consider the competition with neutron emission to the ground or first excited states which is much more sensitive to the differences between the spin-parity distributions . In addition, in the case of actinides, one may need to distinguish between gamma rays originating from the fission fragments and radiative capture gamma rays. This can make radiative capture measurements extremely complicated. Therefore, as a first step we have chosen to investigate the validity of the surrogate method for radiative capture reactions on rare earth nuclei. In particular, our aim is to study the transfer reactions 174 Yb ( 3 He,pγ) 176 Lu and 174 Yb ( 3 He, 4 Heγ) 173 Yb as surrogate for
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tron binding energy in the CN. Therefore, for a fixed beam energy, the surrogate method enables the determination of cross sections over a wide range of corresponding neutron energies. In a direct neutron measurement with a monoen- ergetic neutron beam one we would have needed 4 different targets and several beam energies. Moreover, compared to neutron measurements, surrogate experiments profit from the high intensities of light charged particle beams which reduce considerably the beam time requirements and per- mit the use of thin targets. The measured fission probabil- ities are translated into the associated neutron-induced fis- sion cross sections by multiplying the experimental fission probability with the corresponding calculated CN cross sec- tion, as indicated by eq. 1. The latter was obtained with a Lane-consistent semi-microscopic  deformed  optical model potential built using deformed radial nuclear den- sities calculated in the Hartree-Fock-Bogoliubov frame- work with the Gogny D1S interaction . The error as- sociated with the CN cross section is about 10%. Fig. 3 shows the fission cross section of 231 Pa obtained from the
For the surrogate-reaction method to give cross section results in agreement with those obtained in direct measurements, several conditions have to be fulfilled . First, both the neutron-induced and the surrogate reactions must lead to the formation of a compound nucleus. In that case the decay of nucleus A ∗ is independent of the entrance channel, and the reaction cross section can be factorized into the product of the compound-nucleus formation cross section and the decay probability. The second condition is that the decay probability measured in the surrogate reaction has to be equal to the decay probability in the neutron-induced reaction. This is the case in at least two limiting situations: if the angular momentum ( J ) and parity (π ) distributions populated in the neutron- and transfer- induced reactions are the same, or if the decay probability of the compound nucleus is independent of its angular momentum and parity, which is the so-called Weisskopf- Ewing limit. Since for most surrogate reactions it is not yet possible to determine the populated J π distribution , the validity of the surrogate method has to be verified “a posteriori”, by comparing the obtained results with well known neutron-induced data.
In the recent coral reef literature (re - viewed below) and elsewhere, the word ‘surrogate’ is often used with a ‘pattern- based’ meaning. There are many claims that good surrogates (sensu pattern-based) are identified, but conclusions on effective- ness of pattern-based surrogacy cannot be systemati cally generalized to selection- based surrogacy. This caveat is important for managers and funding agencies. If they aim for a conservation objective using deci- sion support methods such as systematic conservation planning, they should fund studies that are articulated around a con- servation plan, and not ecological studies that statistically quantify links be tween variables. This plan can be quite specific, as the local conservation objectives can also be quite specific as well. Therefore, using the published pattern-based conclu- sions from one site (or region), to identify a conservation area network for another site (or region), is not a recommended practice. As mentioned by Grantham et al. (2010, p. 8), ‘insights into surrogates could be gained from reviewing aspects of the ecol- ogy and biogeography of species that both support the use of surrogates’, or in other words, it is useful to identify beforehand the specific aspects of species (e.g. their rarity) that make surrogates effective or ineffective. This also suggests that demon- strated efficient pattern-based surrogates could be used to develop selection-based surrogacy strategies. But, as highlighted here, effectiveness of both cannot be guar- anteed. Methods for assessing the effec- tiveness of pattern-based and selection- based surrogates are different, which makes both types of surrogates not neces- sarily transposable. According to Williams et al. (2006), who discussed this in depth, Fig. 2. Selection-based surrogacy effectiveness measured for fictive
Surrogate model inﬁll processes may be performed after ignoring missing data in the DoE, whether it is MAR or otherwise. However, when an inﬁll design evaluation fails, the process will fail: if no new data is added to the model, the inﬁll criterion, be it based on y, ^ s 2 , E[I(x)], or some other surrogate based criterion, remains unchanged and the process will stall. The process may be jump started by perturbing the prediction with the addition of a random inﬁll point (a succession of random points may be required before a feasible design is found). However, ignoring this missing data may lead to distortions in the surrogate model, causing continued reselection of infeasible designs and the majority of the sampling may end up being based on random points. As such, because failed design evaluations are not MAR we should impute values to the missing data before training the model.
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In China, such market distortions may result from the CCP involvement in government, or the fact that the government owns four of the largest banks in the world. Even with the expiration of Article 15(a)(ii) of the Accession Protocol, China remains a member of the WTO agreement and is subject to the requirements of the GATT and the ADA. Under the agreements, a WTO Member that seeks to employ the surrogate country method against China would first demonstrate that the product it is investigating lacks comparable prices in China’s domestic market. They can prove this fact by pointing to any of the discrete ways in which the government is involved in China’s economy and buildI0K the case for a causal link from those interventions to the distortion. Once the chain is developed, the WTO Member would rely on Article VI:1 and Article 2 of the ADA to disregard those prices because they are not comparable. Next, the Member would point to the “particular market situation” language as the basis for employing the surrogate country method.
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Taking the consideration above in mind, we adopted the Kriging model to create an approximate functional relationship between the design objective and design parameters to replace the expensive reanalysis of the stent dogboning ratio and radial elastic recoil. The optimization iterations are based on the approximate relationship between the design objective and design parameters to reduce the high computational cost. An adap- tive optimization method based on the Kriging surrogate model combing with modified rectangular grid (MRG) approach was proposed to minimize the radial elastic recoil and the dogboning effect of stent during the expansion process. Expected improvement (EI) function is employed in the adaptive process , which can balance local and global searches and then find the global optimal design even with a small sample size. The FEA solver of ANSYS was used to analyze the measurements of stent expansion performance.
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Measurements based on disease behavior during treat- ment may similarly demonstrate clinical benefit and may be appropriate surrogate endpoints for OS. Progression-free survival (PFS) is defined as the time from randomization to tumor progression or death. The US Food and Drug Admin- istration (FDA) favors PFS as a surrogate endpoint because it accounts for patients who die following tumor progression or following adverse events related to treatment. 6 Time to
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To aid comparison we used the test suite for which we have previously benchmarked our evolutionary approach against all the principal methods and reported improved perfor- mance . Thus, if we can achieve beneﬁts from using surrogate models within a similar algorithmic framework to that paper, we are improving on the state of the art. The test set contains 32 representative tables created by the UK Oﬃce for National Statistics and is publicly avail- able 1 . These vary in size from 1000 to 20,000 cells and have diﬀerent dimensionality, levels of hierarchy, proportions of initially sensitive cells, and proportions of zero cells (which also inﬂuence instance hardness since they provide no ben- eﬁt from suppression). The permutation problems range in size from length 50 to 1928.
by which is the surrogate’s effort in this case. Effort is costly and the cost is given by . Effort of the surrogate is not observable and hence not contractible. After the gestation period is over outcome of the process is realized. The outcome can be ‘high’ which is nothing but the birth of a normal child and we denote it by = 1 . The outcome might also be ‘low’ which can be interpreted as failure of the surrogacy process (might lead to a birth of a defective baby or a ‘still’ baby or otherwise) that can be denoted as = 0 23 . The outcome is observable and hence contractible. In case of success the intended parents get a fixed utility > 0 from having a biological baby and gets 0 if the process fails. We assume that that the surrogate is altruistic and receive a non-pecuniary benefit (warm-glow) of from successfully helping out the intended parents where λ > 0 . If λ > 1 then the surrogate is very altruistic and derives more pleasure than the intended parents. Also we assume for simplicity that in case of a failure the surrogate does not get any altruistic pleasure. The surrogate is assumed to have an outside option denoted by
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premalignant lesions. These have been summarized in a recent systematic review 8 . 956 cases of oral potentially malignant disorders (OPMD) and 675 controls were included in the analysis. In all 19 cross sectional studies, HPV was seen in a higher proportion of the OPMD groups than in the controls (OR 3.87 (95% CI: 2.87–5.21). This association was even more significant with a subgroup analysis of cases of OED (OR 5.10; 95% CI: 2.03–12.80). These findings were confirmed in a second systematic review 7 . While most studies have used polymerase chain reaction (PCR) or in-situ hybridization (ISH), for the detection of HPV DNA, detection of p16 INK4a protein overexpression by immunohistochemistry has also been shown to be a surrogate marker of HPV infection 16-19 .
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Islam generally supports extracorporeal fertilization as it is believed that this process is similar to natural fertilization but it is allowed only under two conditions: sperm and oocyte have to belong exclusively to a husband and wife between whom a marriage agreement (nikah) has been concluded; after fertilization outside a living organism, an oocyte has to be transferred into a mother’s uterus, i.e. that of a woman’s whose oocyte has been fertilized. The use of such concepts as “donor sperm”, “donor oocyte”, and much less “surrogate maternity” is strictly prohibited, comparable to adultery and generates a significant number of social problems. Persons involved in this in any way, if they have not complied with the two conditions above, are committing a sin and are subject to punishment .
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Lastly, the “who you work with” factor is mainly about doing the procedure through an agency or independently. In some countries, agencies that specialize in Surrogacy will have their own legal advisors or lawyers to take care of the legal matters such as the contents of the agreement. With Surrogacy that is done independently, the intended parents and the Surrogate usually only work with a Surrogacy lawyer and a fertility clinic to complete their Surrogacy process. Independent Surrogacy usually costs a lot less than an agency specializing in it, but it requires much more work and legal and/or health risks for the intended parents since they have to handle all the aspects of Surrogacy themselves without the professional guarantee of an agency.
Delivery of activated forms of AKT and Nras via a transposon system into mouse hepatocytes has been shown to induce rapid HCC growth in FVB/N mice . Although activating Ras mutations are seldom found in human HCC samples, simultaneous activation of Akt/ mTOR and Ras/MAPK pathways is often found in hu- man HCC . Previous studies examining the potential and roles of AKT and RAS in HCC induction have shown that activated AKT alone required nearly 30 weeks to induce HCC formation  whereas activated RAS alone was not able to induce HCC formation but caused hepatocyte senescence in immunocompetent mice . The Akt/mTOR pathway involves in lipogenesis, which also promotes the development of HCC [9, 11]. We therefore adopted the Akt/N-Ras-based HDI technology  to establish a novel HCC mouse model expressing lu- ciferase and surrogate tumor antigens (Ags) to monitor tumor growth non-invasively. Tumor progression in this HCC model was found to be more rapid than that in most of the chemically induced and genetically modified models. Both diffuse and nodular types of HCC were observed to develop in this model. We were able to characterize the exhausted state of TAA-specific CD8 + T cells and immunosuppressive cell populations in the TME in the model, indicating that it can be a suitable preclinical model for exploration and evaluation of immune check- point inhibitors and cell-based immunotherapies for HCC treatment.
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The left part of Figure 1 represents the desired neutron-induced reaction on the target A-1, which leads to the compound-nucleus A at an excitation energy E*. The nucleus A can decay through dif- ferent exit channels: fission, neutron emission, etc . . . On the right part of Figure 1, in the surrogate reaction method, the same compound nucleus A is produced by a transfer reaction between a projectile y (a light charged particle) and a target X. In the exit channel of the transfer reaction (y + X → A + w) we have the heavy recoil nucleus A and an outgoing particle w (proton, deuton, triton, etc). The iden- tification of the ejectile w permits to determine the mass A and charge Z of the decaying nucleus. In addition, we can deduce the excitation energy E* of the compound nucleus A by measuring the kinetic energy and the emission angle of the ejectile w. Experimentally, the detection of the ejectile w, in coincidence or not, with a given decay product (e.g., fission fragments or gammas) of the compound nucleus A* gives the decay probability P A deca ,exp y (E ∗ ) of the given reaction channel. According to the sur- rogate reaction method, the measurement of the fission or capture probability permits to determine the neutron-induced cross section for the nucleus A-1 as follows:
Many documents have been written on multidisciplinary optimization in conceptual design and on the integration of surrogate models in this. Kroo et al.  decompose the problem into two levels: a system level whose responsibil- ity is the coordination of the optimization process, and a lower level made up of sub-spaces for the various technical disciplines. Antoine and Kroo ,  linked the different technical disciplines of engine performance, using a Nelder- Mead  algorithm in reference  and a genetic algorithm in reference . It is also worth mentioning the applications by Schumacher et al.  on the structural design of a wing box, by Piperni et al  on the design of business jets, and by Queipo et al.  on the multi-objective design of a liquid-rocket injector. Price et al  included aspects of an aircraft design which are not easily modeled, such as the cost associated to fabrication and maintenance. A recent review on the subject has been recently published by Forrester and Kean .