|Fig. 30 |Structure of the silsesquioxane-bound dinuclear rhodium (II) | | |complex [Rh2((()2(((O2CR)2], where (( ( bridging ortho-metalated| | |aryl phosphane ligand. This complex, anchored to mesoporous | | |silica, is an efficient catalyst for the hydroformylation of | | |styrene (Hydrogen atoms have been omitted for clarity). | |Table 1 |Four categories of single-site heterogeneous catalysts (SSHC). | |Table 2 |Practical applications of single-site heterogeneous catalysts | | |(SSHC). | |Table 3 |Oxyhalogenation of aromatics in air using CuCl16Pc-Na-X and KBr.| |Table 4 |Single-step, highly active and selective nanoparticle catalysts | | |for the solvent-free hydrogenation of polyenes. | |Table 5 |Epoxidation of terpenes using TiIV SSHC on silica under | | |mild conditions. | |Table 6 |Activities, selectivity (for methyl mandelate) and enantiomeric | | |excess (ee) for the various homogeneous and heterogeneous Rh(I) | | |catalysts are summarized for the asymmetric hydrogenation of | | |methyl benzoyl formate. Reaction conditions: substrate ( 0.5g; | | |solvent (methanol) ( 30 ml; homogeneous catalyst ( 10 mg; | | |heterogeneous catalyst ( 50 mg; Pressure = 20 bar; temp = 313 K;| | |time = 2 h | |Table 7 |Asymmetric hydrogenation data for the Pd(II) catalysts. For | | |E-(()-phenylcinnamic acid (PCA) the reactions were carried out | | |for 24 hrs and for methyl benzoyl formate (MBF) the reactions | | |were carried out for 2 hrs. (See Table 5 for reaction | | |conditions). | |Table 8 |A summary of the economically significant catalytic conversions | | |effected by single-site, open-structure alumino-silicate and | | |alumino-phosphate (zeolitic) solids | |Table 9 |The advantages of Single-Site Heterogeneous Catalysts (SSHC) |
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Although not randomized, this is the first detailed prospective assessment of the R-LESS technique in performing LDN. Although our numbers are small, we publish these results as an indicator of quality for our novel technique and demonstrate modest but significant benefits in this population of young healthy patients, who may engender benefit from a cosmetically superior operation. A limitation was that we were not able to blind the patients immediately pre- op or post-op (with abdominal binders to mask the scars), however this may be what is needed to truly create a randomized trial in the future. However, we did not emphasize that one technique was more beneficial than the other during the consent process so as to minimize patient bias. It has been our hope that the minimally invasive nature of this technique would increase the appetite for healthy active individuals to participate in living donation. In fact, it is of interest that the availability of R-LESS technique has been associated with an increased interest in living donation by potential donor patients at our institution. Furthermore, we hope that our excellent preliminary results will encourage other groups to assess R-LESS donor nephrectomy as a part of multi-centred prospective study to firmly establish the procedure as a reasonable option for donor nephrectomy. With the advancement of robotic platforms intended for single incision surgery by companies such as Titan Medical TM and Intuitive Surgical ®, the role of robotic surgery in donor nephrectomy should be re-assessed on a continuous basis.
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inserted through the curved cannula, and the robotic system provided a switching motion between right-hand and left- hand orientations to improve the surgeon’s ergonomics. The assistant surgeon performed gallbladder traction toward the lateral and upward direction to expose Calot’s triangle. After dissecting around the GB neck and cystic duct, the cystic duct and cystic artery were ligated securely by intracorpo- real tie ligation and a Hem-o-lok clip and then divided with robotic scissors. Compared to laparoscopic single-port sur- gery, the robotic single-port surgical system provided a sta- ble environment to perform intracorporeal tie ligation, de- spite the absence of EndoWrist movement. Additionally, the robotic single-port surgical system has a special feature, called Intraoperative Firefly TM Fluorescence Imaging. This
Activation of TLR9 by direct injection of unmethylated CpG nucleotides into a tumor can induce a therapeutic immune response; however, Tregs eventually inhibit the antitumor immune response and thereby limit the power of cancer immunotherapies. In tumor-bearing mice, we found that Tregs within the tumor preferentially express the cell surface markers CTLA-4 and OX40. We show that intratumoral coinjection of anti–CTLA-4 and anti-OX40 together with CpG depleted tumor-infiltrating Tregs. This in situ immunomodulation, which was performed with low doses of antibodies in a single tumor, generated a systemic antitumor immune response that eradicated disseminated disease in mice. Further, this treatment modality was effective against established CNS lymphoma with leptomeningeal metastases, sites that are usually considered to be tumor cell sanctuaries in the context of conventional systemic therapy. These results demonstrate that antitumor immune effectors elicited by local immunomodulation can eradicate tumor cells at distant sites. We propose that, rather than using mAbs to target cancer cells systemically, mAbs could be used to target the tumor infiltrative immune cells locally, thereby eliciting a systemic immune response.
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Differences observed in assays utilizing laboratory-constructed mutants may be obscured during infection by changes elsewhere in the genome. Accordingly, we assayed clinical agr-defective strains using a small set of genotypically diverse agr- defective MRSA clones initially obtained from mixed cultures containing agr-positive and agr-negative cells (51). Strains were previously genotyped to conﬁrm that variants within a single specimen were otherwise isogenic (51). That work also traced the basis of agr dysfunction to inactivating mutations in agrA or agrC. Of the 4 clinical isolates in our collection that were susceptible to gentamicin, 2 genotypically distinct clones (see Table S1 in the supplemental material) exhibited 10-fold protection from killing by gentamicin (Fig. 5C and D). Thus, the data are consistent with data from laboratory strains indicating that agr inactivation reveals cryptic genetic variation among strains in their response to lethal stress. Moreover, variation in intrinsic (wild-type) tolerance was also observed. The mechanisms underlying strain-dependent differences in agr- mediated and intrinsic tolerance to lethal stress are unknown. Future work will inves- tigate to what extent they are stress speciﬁc.
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robotic single-site (RSS) sacrocolpopexy, and I found this procedure to be feasible and safe. All RSS procedures were completed suc- cessfully. The mean operative time was 122.17±22.54 minutes, and the mean blood loss was 66.67±45.02 mL. No operative or major postoperative complications occurred. Additional studies should be performed to assess the benefits of RSS sacrocolpopexy. I pres- ent the first six cases of da Vinci Single-Site ® surgery in urogynecology and provide a detailed description of the technique.
investigate the utility of DSC in discerning changes in HSA that occur when the protein is specifi- cally adducted, and determine how adduct formation manifests itself in HSA denaturation curves, or thermograms, measured by DSC. Effects of site specific covalent attachment of biotin (the ad- duct) on the thermodynamic stability of HSA were investigated. Each of the HSA preparations were modified by biotinylation targeting a single site, or multiple sites on the protein structure. Ther- mograms of both modified and unmodified HSA samples successfully demonstrated the ability of DSC to clearly discern the two HSA preparations and the presence or absence of covalent modifi- cations. DSC thermogram analysis also provided thermodynamic characterization of the different HSA samples of the study, which provided insight into how the two forms of HSA respond to cova- lent modification with biotin. Consistent with published studies  HSA 96 , the preparation with
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Geotourism is a new phenomenon, which has emerged in the tourism literature during the past two decades, and whose meaning suﬀ ered from global census. Geotourism is still a new discipline and relatively little has been written about its demand side, demonstrated by a lack of studies in the literature This article studies the recreational value of geotourism areas, and focuses on the ﬁ rst geopark in the Czech Republic, namely the Czech Paradise Geopark. To assess the recreational value the travel cost method is applied, speciﬁ cally the individual travel cost model. The necessary research data was gathered through intensive tourist surveys conducted in the study area. Data gathered in the respondents’ survey served to determine the consumer surplus as a measure of recreational value and to develop the single site travel cost model. The dependent variable in the conducted model is the number of visits in the area and among the independent variables, studied age, education, travel cost, family status, economic activity and income. The results were subsequently compared to ﬁ ndings in the available literature, research works and case studies.
The molecular events that mediate cholecystokinin (CCK)-stimulated pancreatic secretion are not well defined because of the complex receptor-binding and concentration-response characteristics of this hormone. Functional models of receptor occupancy initiating the cascade leading to secretion have been complicated by the inhibition of secretion effected by supramaximal concentrations of CCK. Recent report of a CCK analogue that does not exhibit supramaximal inhibition led us to synthesize a similar analogue that could also be radiolabeled for studies of receptor binding and affinity labeling, and for studies of second messenger activity. This probe, D-Tyr-Gly-[(Nle28,31)CCK-26-32]-phenethyl ester, was a fully efficacious secretagogue with no supramaximal inhibition, and, unlike native hormone, bound to a single class of sites present on both acini and membranes. Occupation of this site correlated well with stimulation of secretion. Evidence that this was indeed a CCK- binding site were the abilities of CCK and the antagonist L-364, 718 to inhibit binding of this analogue. Affinity labeling confirmed the identity of the site mediating secretory stimulation as a Mr = 85,000-95,000 protein. Whereas the nonhydrolyzable guanosine triphosphate analogue, 5'-guanylyl-imidodiphosphate, was a potent inhibitor of CCK binding, it had no effect on binding of this secretagogue, suggesting that a novel cascade not involving a guanine nucleotide-binding protein mediates CCK stimulation of pancreatic secretion.
Recently, flavone analogs, each varying only in the 6-position substituent, were compared. Whole-cell patch-clamp and animal behavior experiments demonstrated 6-bromoflavone to be a positive modulator at GABA type A receptors, act- ing via a flumazenil-sensitive high-affinity benzodiazepine binding site. In contrast, 6-fluoroflavone and 6-chloroflavone were found to be neutralizing modulators. In patch-clamp studies, 6-hydroxyflavone displayed a significant preference for α 2-containing and α 3-containing subtypes, which were thought to mediate the anxiolytic effect, compared with α 1- and α 5-containing subtypes expressed in HEK 293T cells. In mice, 6-hydroxyflavone exhibited anxiolytic-like effects unaccompanied by the sedative, cognitive impairment, myo- relaxant, motor incoordination, and anticonvulsant effects commonly associated with classical benzodiazepines. 102
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However, some assistance can be gleaned from a handful of existing survey-based studies examining how landowners think about public access to their rural green spaces (Teasley et al., 1997; Gentle et al., 1999; Wright et al., 2002), albeit that most of these studies have related to the US experience (and its different topographic and legislative context) and therefore may not be directly indicative of UK motives and meaning-making. These US studies were motivated by a concern by policy-makers that, even after legislative concessions had been made at state and federal level, rural landowners were still using stated fears of liability as a reason for prohibiting recreational access to their land. This implied at best that the owners were struggling to understand the applicable liability rules and at worst that such behaviour was the product of a wilful desire by owners to misinterpret (to themselves) or misrepresent (to their audience) the impact of liability-risk upon their site access decision-taking. In short, that it was a cover for some other motivation.
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Using SCADS, a computationally guided design approach, Naq was incorporated into the helix of a miniprotein, NaqCage (Chapter 4). The NaqCage is based upon the 20- residue TrpCage, which has a compact hydrophobic core surrounding a buried Trp residue. By replacing this Trp, the NaqCage was designed to stably incorporate Naq in a similar structural context, allowing investigations on the effects a well-packed protein environment on its redox chemistry. While the initial computational designed target was not appreciably structured due to destabilization of the helix by Naq, the NaqCage was iteratively redesigned by hand to a point where a solution structure could be determined. Analysis of the NMR data was complicated by several factors, but nearly all of the backbone protons have been assigned and further analysis may yield a structure. This would be the first report of stably incorporating another amino acid at the site of the Trp, but more importantly this work generated a water-soluble, synthesizable framework for testing the effects of hydrogen bonding and electrostatic interactions on Naq’s redox chemistry in an aqueous environment – a crucial set of information that is woefully lacking in the literature.
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arrays 23–26 . The main characteristics of these site-controlled QD fabrication techniques are reported in Table 1. For the sake of completeness, we mention that up to now strong coupling was not yet observed in site-controlled QDs coupled with photonic cavities, to the best of our knowledge. Other approaches to the fabrication of site-controlled QDs, for which the integration with PhC cavities is still to be demonstrated, include the self-organization of individual InAs QDs by scanning tunneling probe-assisted nanolithography 27 ; the “vicinal substrate” approach 28 ; the nucleation of InAs QDs on strain modulated buffer layers grown on submicron mesa array 29 ; and quantum well
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The main goal of this research is to find a single-site catalyst system, which can form copolymers of ethylene and methyl acrylate. Single-site catalysts represent the most recent generation of Ziegler/Natta catalysts, which in contrast to the latter only form one active catalytic species. Copolymers of ethylene with polar monomers are used as adhesives, paints and compatibilizers. Historically, these copolymers have only been prepared by free-radical copolymerization. Now there is potential for the use of coordination systems as well (i.e. single-site catalyst). Single-site catalysts not only provide an excellent control over tailoring properties of polyolefin but also provide better incorporation with higher yields. The single-site catalysts based on late transition metals appear to be more stable towards polar group monomers. For our experiment we are considering a modified metallocene catalyst, an iron based bis(imino)pyridine catalyst and a nickel(II)enolate. Our work also includes characterization of the copolymers by IR,
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In this study, we test the effect of changes in accelerometer location in a single-site, tri- state classification paradigm. This study attempts to emulate the performance of an MMG classifier trained with the accelerometer in one location and then deployed in a slightly different location. MMG signals were simultaneously recorded by accelerome- ters located at, and radial to, the belly of the flexor carpi radialis muscle while partici- pants held their hand in the extended, flexed, and semi-pronated positions. The classifier, trained using features from the reference accelerometer (located over the mus- cle belly) to maximize three-class classification accuracy, was tested with features from the longitudinally and transversely displaced accelerometers. The emphasis of this study is not the classification method per se, but rather the effect of accelerometer displace- ments in a typical MMG signal classification paradigm. A single MMG channel is there- fore used instead of the added information and higher classification accuracy afforded by monitoring multiple muscle sites .
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In our structural proteomics lab, site-directed mutagene- sis, truncation and deletion mutagenesis are routine methods used by variety of personnel with different exper- tise in molecular biology. Although most problems with QuikChange™ can be overcome with modification or refinement, we encountered problems in mutation of low GC sequences from cloned Sulfolobus islandicus rudivirus (SIRV) CAG38830 and CAG38833  which we were unable to solve. These problems led us to consider a mod- ification to QuikChange™ that would preserve its simplic- ity but enhance its efficiency and applicability. Our modified method uses primers containing extended non- overlapping sequences at the 3' end (significantly larger than suggested in ) and primer-primer complemen- tary sequences at the 5' end (Figure 2). We used this mod- ified method to make various mutations, including insertions (18 residues) and deletions (25 residues) in a cloned vraR gene of methicillin resistant Staphylococcus aureus (MRSA) . We have also used four primers to create multiple-site mutations, deletions and insertions. This modified procedure has proven to be highly efficient.
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Approaches to Structural Health Monitoring may be broadly separated into two classes: data-based approaches that follow a statistical pattern recognition paradigm and rely solely on experimental data; and model-based approaches that make use of the predictions of a representative physics-based model of the structure, typically by applying a Finite Element (FE) model updating procedure. While the problem of multiple damage location from a purely data-based perspective has received very little dedicated attention in the literature, FE model updating is, at least in principle, appropriate to the multiple damage location task. The solution procedure typically involves minimisation of residuals between damage-sen- sitive features drawn from the experimental structure and the predictions of the model. Ruotolo and Surace  presented an early study of this type focusing on multiple damage location and assessment in a cantilever beams, with a weighted sum of modal features (natural frequencies, modal curvatures and mass-normalised modeshapes) adopted as the objective function to be minimised. A similar approach, the Multiple Damage Location Criterion (MDLAC), is presented by Contursi et al , with the cross-correlation between measured and theoretical natural frequencies adopted as the objective function and applied to multi-site damage. An incremental development of the MDLAC approach is presented in  with damage location pursued using Dempster-Shafer evidence theory, allowing fusion of the results of frequency MDLAC and modeshape MDLAC outcomes, and a micro-search genetic algorithm used to estimate damage extent.
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Having ultimately determined the long-term behavior of the tit-for-tat population in Site B, we wish to translate these results back into the context of the IPD tournament. We have shown that for small λ, the tit-for-tat population in the middle site thrives and eventually pushes the mean population to extinction. On the other hand, when λ is large, the reverse scenario occurs and tit-for-tat players are driven to extinction. Having seen that there are no stable nontrivial equilibria in the system, we know that for any value of λ one population will eventually dominate the middle site, though this process may take hundreds or thousands of generations.
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To understand why the deletion allele that did not con- tain branchpoint A still produces the normally spliced form, we checked the nearby intron sequence and found two other As located at the seventh and eighth nucleotides from the branchpoint A (Fig. 4a). We performed the branchpoint site prediction analysis using SROOGLE and Human Splicing Finder ; both tools predicted that these two nearby As also lie within the potential consensus branchpoint site sequence and can be used as alternative branchpoints in the deletion allele. We then tested the influence of these two nearby As on splicing using mini- gene constructs (Fig.4). In the wild-type allele, when the two nearby AA were changed to AG or GA, RNA spliced majorly in the normal form; when changed to GG, there was a decrease in the normal form and an increase in the intron inclusion form. In the deletion allele, when both AA were changed to GG, there was a further decrease in the normal form accompanied with a further increase in the intron inclusion form (Fig.4b). These results suggested other As nearby may serve as alternative branchpoints.
Figure 1 Experimental setup and fluorescence imaging. a, Schematic image showing the optical lattice geometry, the 2d quantum gas and the high-resolution objective. The optical lattice setup consisted of two horizontal lattice axes (in the x and y-directions) and a vertical lattice axis (in the z-direction). The latter was created by reflection from a vacuum window with a coating that reflects the lattice wavelength (1064 nm) and transmits the imaging wavelength (780 nm). The 2d quantum gas was prepared in a single anti-node of the vertical lattice and is imaged with the high-resolution objective using fluorescence detection. b, Horizontal lattice depth during a typical experimental sequence. The loading into the square lattice is achieved by quasi-adiabatic s-shaped ramps with a duration of 120 ms. The final lattice depths in x- and y-directions V x , V y were independently controlled. For the detection, the lattice gas is frozen by rapidly increasing the lattice depths to
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