TRADING WITH THE WAITING‐LIST: THE JUSTICE OF LIVING DONOR LIST EXCHANGE

In a Living Donor List Exchange program, the donor makes his kidney available for allocation to patients on the postmortal waiting‐list and receives in exchange a postmortal kidney, usually an O‐kidney, to be given to the recipient he favours. The program can be a solution for a candidate donor who is unable to donate directly or to participate in a paired kidney exchange because of blood group incompatibility or a positive cross‐match. Each donation within an LDLE program makes an additional organ available for transplantation. But because most of the pairs making use of the program will be A/O incompatible, it will also tend to increase the waiting time for patients with blood group O, who already have the longest waiting time. It has therefore been objected that the program is materially unjust, because it further disadvantages the least advantaged. This objection appeals to John Rawls’ difference principle. However, the context for which Rawls proposed that difference principle, is significantly different from the present one. Applying the principle here amounts to a lop‐sided trade‐off between considerations of need and considerations of overall utility. Considerations of formal justice, however, may lead to a stronger objection to LDLE programs. Such a program means that one O‐patient on the waiting list is exempted from the application of the general criteria used in constructing the list because he has a special bargaining advantage. This objection is spelled out and weighed against the obvious attraction of LDLE in a situation of (extreme) organ scarcity.     

The effect of solicitations on grooming exchanges among female Japanese macaques at Katsuyama

In group-living primates, individuals often exchange grooming with not only kin but also non-kin. We investigated the effect of soliciting behaviors on grooming exchanges in a free-ranging Japanese macaque (Macaca fuscata) group at Katsuyama. In this study, we used a focal animal sampling method, targeting 14 females. Data were collected for 15.75 ± 2.67 (mean ± SD) hours per focal female. We classified female–female pairs into three pair types: kin pairs, affiliated non-kin pairs, and unaffiliated non-kin pairs. Females received grooming more frequently when they solicited after grooming their partners than when they did not solicit in all pair types. In addition, females received grooming less frequently when they did not groom their unaffiliated non-kin partners before soliciting; prior grooming was not needed to receive grooming from kin or affiliated non-kin partners. The degree of grooming reciprocity did not differ according to the frequency with which females in kin or affiliated non-kin pairs solicited after grooming. On the other hand, grooming reciprocity between unaffiliated non-kin females was more balanced when they solicited frequently after grooming, as compared with when they did not. In conclusion, our study suggests that soliciting behaviors promote grooming exchanges in female Japanese macaques.     

GPU-accelerated replica exchange molecular simulation on solid–liquid phase transition study of Lennard-Jones fluids

Determining the solid–liquid phase transition point by conventional molecular dynamics (MD) simulations is difficult because of the tendency of the system to get trapped in local minimum energy states at low temperatures and hysteresis during cooling and heating cycles. The replica exchange method, used in performing many MD simulations of the system at different temperature conditions simultaneously and performs exchanges of these temperatures at certain intervals, has been introduced as a tool to overcome this local-minimum problem. However, around the phase transition temperature, a greater number of different temperatures are required to adequately find the phase transition point. In addition, the number of different temperature values increases when treating larger systems resulting in huge computation times. We propose a computational acceleration of the replica exchange MD simulation on graphics processing units (GPUs) in studying first-order solid–liquid phase transitions of Lennard-Jones (LJ) fluids. The phase transition temperature for a 108-atom LJ fluid has been calculated to validate our new code. The result corresponds with that of a previous study using multicanonical ensemble. The computational speed is measured for various GPU-cluster sizes. A peak performance of 196.3 GFlops with one GPU and 8.13 TFlops with 64 GPUs is achieved.     

Simulating seasonal and inter-annual variations in energy and carbon exchanges and forest dynamics using a process-based atmosphere�Cvegetation dynamics model

The present paper shows simulated results of seasonal and inter-annual variations in energy and carbon exchanges and forest dynamics in a sub-boreal deciduous forest using a fully coupled atmosphere?Cvegetation interaction model [multilayered integrated numerical model of surface physics-growing plants interaction (MINoSGI)]. With careful adjustment of site-specific eco-physiological parameters, MINoSGI reproduced successfully stand biomass?Ctree density relationship based on the forest inventory data for 7 years (1999?C2005) and seasonal and inter-annual variations in energy and CO₂ fluxes measured by means of eddy covariance technique for 3 years (2003?C2005) in the sub-boreal forest, northern Japan. In addition, MINoSGI estimated annual evapotranspiration (E _vt) at 328.6 ± 25.8 mm year^?1, net primary production (NPP) at 372.1 ± 31.5 gC m^?2 year^?1 and net ecosystem exchange (NEE) at ?224.2 ± 32.2 gC m^?2 year^?1. We found the estimate of annual NEE in our site lies among the estimates at other forest stands with the almost same climatic conditions in northern Japan, although the tree species and stand age of these forests are different from those of our site. Overall, MINoSGI was found useful to present simultaneous simulations of forest dynamics, surface energy, and carbon exchanges of a forest stand in the future from micro-meteorological and ecophysiological points of view.     

Application of bipolar electrodialysis to E. coli fermentation for simultaneous acetate removal and pH control

The application of bipolar electrodialysis (BPED) for the simultaneous removal of inhibitory acetate and pH control during E. coli fermentation was investigated. A two cell pair electrodialysis module, consisting of cation exchange, anion exchange and bipolar membranes with working area of 100 cm² each, was integrated with a standard 7 l stirred tank bioreactor. Results showed that BPED was beneficial in terms of in situ removal of inhibitory acetate and a reduction in the amount NH₄OH used for pH control. In batch and fed-batch BPED fermentations, base additions were decreased by up to 50% in both cases compared to electrodialysis (ED) fermentations with pH controlled at 6.7 ± 0.1. Consequently, the final biomass (34.2 g DCW l^?1) and recombinant protein (5.5 g l^?1) concentrations obtained were increased by up to 37 and 20%, respectively.     

Inferring the conformation of RNA base pairs and triples from patterns of sequence variation.

The success of comparative analysis in resolving RNA secondary structure and numerous tertiary interactions relies on the presence of base covariations. Although the majority of base covariations in aligned sequences is associated to Watson-Crick base pairs, many involve non-canonical or restricted base pair exchanges (e.g. only G:C/A:U), reflecting more specific structural constraints. We have developed a computer program that determines potential base pairing conformations for a given set of paired nucleotides in a sequence alignment. This program (ISOPAIR) assumes that the base pair conformation is maintained through sequence variation without significantly affecting the path of the sugar-phosphate backbone. ISOPAIR identifies such 'isomorphic' structures for any set of input base pair or base triple sequences. The program was applied to base pairs and triples with known structures and sequence exchanges. In several instances, isomorphic structures were correctly identified with ISOPAIR. Thus, ISOPAIR is useful when assessing non-canonical base pair conformations in comparative analysis. ISOPAIR applications are limited to those cases where unusual base pair exchanges indeed reflect a non-canonical conformation.     

The Flp recombinase cleaves Holliday junctions in trans

The Flp site-specific recombinase is encoded by the 2 µm plasmid of Saccharomyces cerevisiae and is a member of the integrase family of recombinases. Like all members of the integrase family studied, Flp mediates recombination in two steps. First, a pair of strand exchanges creates a Holliday-like intermediate; second, this intermediate is resolved to recombinant products by a second pair of strand exchanges.
Evidence derived from experiments using linear substrates indicates that Flp's active site is composed of two Flp protomers. One binds to the Flp recognition target site (FRT site) and activates the scissile phosphodiester bond for cleavage. Another molecule of Flp bound elsewhere in the synaptic complex ( in trans ) donates the nucleophilic tyrosine that executes cleavage and thereby becomes covalently attached to the 3' phosphoryl group at the cleavage site.
It has previously been shown that Flp efficiently resolves synthetic, Holliday-like (χ) structures to linear products. In this paper, we examined whether resolution of χ structures by Flp also occurs via the trans cleavage mechanism. We used in vitro complementation studies of mutant Flp proteins as well as nicked χ structures to show that Flp resolves χ structures by trans cleavage. We propose a model for Flp-mediated recombination that incorporates trans cleavage at both the initial and resolution steps of strand exchange.     

Evaluation and Allocation of Greenhouse Gas Reductions in Industrial Symbiosis

Industrial symbiosis (IS) exchanges have been recognized to reduce greenhouse gas (GHG) emission, though methods for quantification of GHG emissions in IS exchanges are varied, and no standardized methods are available. This article proposes a practical approach to quantify total and allocated GHG emissions from IS exchanges by integrating the GHG protocol and life cycle assessment. The proposed method expands the system boundaries to include all IS companies, and the functional flow is set to be the sum of the main products. The total impact of a company is allocated to the main product. Three by‐product impact allocation methods of cutoff, avoidance, and 50/50 are proposed, and the total and distributed impacts of the IS systems in an industrial park are theoretically derived. The proposed method was tested to quantify GHG reduction in a real IS exchange developed between Korea Zinc (a zinc smelter) and Hankook Paper (a paper mill company) in the Ulsan Eco‐Industrial Park initiative. The total reduction of GHG emissions in this IS exchange, 60,522 tonnes of carbon dioxide per year, was the same in the GHG protocol, whereas GHG distribution between two companies depended on the allocation method. Given that the reduction of GHG emissions from IS exchanges is the product of the collaboration of giving companies and receiving companies, the 50/50 allocation method is best from an equivalent‐responsibility and benefit‐sharing perspective. However, this study suggests a more practical implementation approach based on a flexible and negotiable method of allocating the total GHG reduction between stakeholders.     

Kynurenic acid in human renal cell carcinoma: its antiproliferative and antimigrative action on Caki-2 cells

Kidneys possess a complex enzyme system which plays a major role in tryptophan metabolism. Taking into account a considerably high concentration of one of the tryptophan metabolites, kynurenic acid (KYNA) in this organ and previously reported antiproliferative activity against colon cancer cells in vitro, we measured its content in human normal and tumour kidney tissue. KYNA concentration was considerably higher in normal renal tissue (379.7 ± 39.7 pmol/g wet weight) than in renal cell carcinomas (115.5 ± 20.8 pmol/g wet weight). In in vitro experiments, KYNA in higher micro- and millimolar concentrations significantly inhibited proliferation, DNA synthesis and migration of renal cancer Caki-2 cells. Our results suggest that KYNA may affect cell cycle regulators and signalling pathways through overexpression of p21 Waf1/Cip1 and inhibition of phosphorylation of Rb protein and p38 MAPK. In conclusion, KYNA may be suggested as an endogenous agent, controlling the growth of tumour, or a chemopreventive agent.     

Molecular dynamics simulation to investigate anhydrous phosphoric acid-doped polybenzimidazole

The study conducted a molecular dynamics simulation based on a condensed-phase optimised molecular potentials for atomistic simulation studies force field model to investigate an anhydrous system of phosphoric acid-doped polybenzimidazole (poly[2,2′-(m-phenylene)-5,5′-bibenzimidazole], PBI). Intermolecular pair correlation functions and corresponding coordination numbers were calculated to research the strengths for various types of hydrogen bonding. The results display that the strengths of the hydrogen bonding interactions are in the order of o1–h pair > o2–h pair > n2a–h pair > n3a–h pair, and most protons are located around the neighbourhood of H₂PO₄^– rather than that of PBI. The proton conductivities are 3.86 × 10^?3 S cm^?1 at 298 K and 8.50 × 10^?3 S cm^?1 at 413 K. Moreover, the value obtained from our simulation system at 413 K is within the same order of magnitude as the experimentally measured value 0.012 S cm^?1 at 420% doping level. The distribution of proton displacement exhibits that the displacement of most protons is about 1.25–2.5 Å. The displacement is over 3.0 Å only for a fraction of protons. In addition, the greatest displacement can approach 4.595 Å. The trajectory analyses of protons show that the most possible mechanisms of proton transfer come from three ways: (a) between two H₂PO₄^– anions, (b) between H₂PO₄^– anions and benzimidazole moieties and (c) between two benzimidazole moieties. The dynamics of polymer motion was studied by the trajectory analyses of ring flips. The large amplitude flips of rings in the polymer chains were found in the system. The flips between benzene and benzimidazole are more frequent than that between benzimidazole moieties.     

Investigation of rubidium(I) ion solvation in liquid ammonia using QMCF-MD simulation and NBO analysis of first solvation shell structure

Rb(I) ion solvation in liquid ammonia has been studied by an ab initio quantum mechanical charge field molecular dynamics simulation, and the first solvation shell structure has been analyzed using natural bond orbital. The simulation was performed for an ion and 593 ammonia molecules in a box with a length of 29.03 Å corresponding to a liquid ammonia density of 0.69 g/mL at 235.16 K. The quantum mechanical calculation was carried out for atomic interactions in the radius of 6.4 Å from the ion using LANL2DZ ECP and DZP (Dunning) basis sets for Rb(I) ion and ammonia respectively. The trajectories of the simulation were analyzed in terms of radial, angular, and coordination number distribution functions, vibration, and mean residence time (MRT). Two solvation shell regions are observed for the Rb(I)-N as well as the Rb(I)-H. The maximum distance of Rb(I)-N in the first solvation shell is in accordance with experimental data where a coordination number of 8 is favorable. A non-single coordination number of the first and second shell indicates dynamic solvation structure. It is confirmed by frequent exchange ligand processes observed within a simulation time of 15 ps. The low stabilization energy of donor acceptor ion-ligand interaction with a small Wiberg bond index affirms that the Rb(I)-NH₃ interaction is weak electrostatically.     

Specificity of origin recognition by replication initiator protein in plasmids of the pT181 family is determined by a six amino acid residue element.

We have investigated the specificity of replication origin recognition by the initiator proteins of a set of six closely related Staphylococcus aureus plasmids, the pT181 family. These plasmids replicate by an asymmetric rolling-circle mechanism using plasmid-coded initiators that nick the replication origins and form a phosphotyrosine bond at the 5' nick terminus. Five of the plasmids are in different incompatibility groups and their initiator proteins do not cross-complement the cloned origins of any but their own plasmid. One pair is weakly incompatible and their initiator proteins and origins do cross-complement for replication in vivo. This pattern of cross-reactivity led to the prediction that the determinant of specificity would correspond to a homologously positioned set of six residues in the C-terminal domain of the protein, some 80 residues away from the active site tyrosine, that are divergent for all of the compatible plasmids and identical for the incompatible pair. Site-directed mutagenesis was used to exchange these six residues among three pairs of plasmids and these exchanges brought about the predicted switching of origin recognition specificity. Single substitution within this six residue set reduced or eliminated the activity of the protein but did not alter the origin recognition specificity. These six and flanking residues cannot form an amphipathic alpha-helix nor do they conform to the classical helix-turn-helix or other known DNA binding motifs. A novel type of interaction is suggested in which the protein binds to its recognition site, bends and melts the DNA, and causes or enhances the extrusion of an adjacent cruciform containing the nick site. This configuration would juxtapose the nicking target and the active site tyrosine residue and would unwind the highly G + C-rich replication origin.     

Profiling expression of lipoxygenase in cucumber during compatible and incompatible plant-pathogen interactions

We compared lipoxygenase (LOX) expression in cucumber in response to host and non-host pathogens. Our results displayed significant difference in expression of LOX between compatible and incompatible interaction at 12, 24 and 48 h after inoculation. Moreover, LOX expression at 72 h after inoculation was similar in both compatible and incompatible interaction. It seems that early induction of LOX plays a crucial role in plant defense against pathogens.     

Light and soil moisture effects on biomass and its allocation in Osmorhiza depauperata Philippi (Apiaceae)

Changes in forest openings affect light quality and quantity, and the magnitude of rainfall that reaches the soil surface. Osmorhiza depauperata, a geophyte, acclimates to changes imposed because of forest openings. We studied which changes in biomass allocation allow acclimation of O. depauperata to the various environments that this species inhabits, and where it develops better. Three light intensities (I4 = 4 %, I26 = 26 %, I64 = 64 % of ambient sunlight) and two moisture levels (M40 = 40–60 %, M80 = 80–100 % field capacity) were evaluated on O. depauperata under greenhouse conditions. Plant biomasses per pot were 0.81, 0.56 and 0.48 g at I26, I4 and I64 light intensities, respectively, after one growing season. The biomass allocation to aboveground tissues and leaf area decreased as light intensity increased. Soil moisture modified only belowground biomass and weight of fine roots. The interaction between soil moisture content and light intensity was consistent. This was because of a significant reduction in total plant biomass under high both soil moisture content and high light intensity. Osmorhiza depauperata growth was favored most at medium light intensities. Changes in biomass allocation among various organs allow this species to inhabit forest habitats with different light intensities.     

Kidney cancer mortality and ionizing radiation among French and German uranium miners

The investigation of potential adverse health effects of occupational exposures to ionizing radiation, on uranium miners, is an important area of research. Radon is a well-known carcinogen for lung, but the link between radiation exposure and other diseases remains controversial, particularly for kidney cancer. The aims of this study were therefore to perform external kidney cancer mortality analyses and to assess the relationship between occupational radiation exposure and kidney cancer mortality, using competing risks methodology, from two uranium miners cohorts. The French (n = 3,377) and German (n = 58,986) cohorts of uranium miners included 11 and 174 deaths from kidney cancer. For each cohort, the excess of kidney cancer mortality has been assessed by standardized mortality ratio (SMR) corrected for the probability of known causes of death. The associations between cumulative occupational radiation exposures (radon, external gamma radiation and long-lived radionuclides) or kidney equivalent doses and both the cause-specific hazard and the probability of occurrence of kidney cancer death have been estimated with Cox and Fine and Gray models adjusted to date of birth and considering the attained age as the timescale. No significant excess of kidney cancer mortality has been observed neither in the French cohort (SMR = 1.49, 95 % confidence interval [0.73; 2.67]) nor in the German cohort (SMR = 0.91 [0.77; 1.06]). Moreover, no significant association between kidney cancer mortality and any type of occupational radiation exposure or kidney equivalent dose has been observed. Future analyses based on further follow-up updates and/or large pooled cohorts should allow us to confirm or not the absence of association.     

Morphophysiological,ultrastructural, and nutritional changes induced by Cu toxicity in young Erythrina fusca plants

Erythrina fusca is an important legume used for shade cover in cacao plantations in Brazil. Cacao plantations receive large quantities of copper (Cu)-containing agrochemicals, mainly for control of diseases. Therefore, Cu toxicity was investigated in seedlings grown in hydroponics with increasing concentrations of Cu (0.005–32 mg L^?1) in a greenhouse. Ultrastructural analyses showed cell plasmolysis in the root cortical area and changes in thylakoid membranes at 8 mg Cu L^?1 and higher. There were changes in epicuticular wax deposition on the leaf surface at the 16 and 32 mg Cu L^?1 treatments. Leaf gas exchanges were highly affected 24 hours after application of treatments beginning at 8 mg Cu L^?1 and higher Cu concentrations. Chemical analyses showed that Cu content in E. fusca roots increased as Cu concentration in the nutrient solution increased, whereas the shoot did not show significant changes. It is also observed that excess Cu interfered with Zn, Fe, Mn, Mg, K, P, and Ca content in the different E. fusca organs. Investigation of Cu toxicity symptoms focusing on morphophysiological, ultrastructural, gas exchange, and nutritional changes would be useful to alleviate Cu toxicity in E. fusca under field conditions, an important agroforestry species in cacao plantation.     

A methyl <Superscript>1</Superscript>H double quantum CPMG experiment to study protein conformational exchange

Protein conformational changes play crucial roles in enabling function. The Carr–Purcell–Meiboom–Gill (CPMG) experiment forms the basis for studying such dynamics when they involve the interconversion between highly populated and sparsely formed states, the latter having lifetimes ranging from ~?0.5 to ~?5 ms. Among the suite of experiments that have been developed are those that exploit methyl group probes by recording methyl ¹H single quantum (Tugarinov and Kay in J Am Chem Soc 129:9514–9521, 2007) and triple quantum (Yuwen et al. in Angew Chem Int Ed Engl 55:11490–11494, 2016) relaxation dispersion profiles. Here we build upon these by developing a third experiment in which methyl ¹H double quantum coherences evolve during a CPMG relaxation element. By fitting single, double, and triple quantum datasets, akin to recording the single quantum dataset at static magnetic fields of B_o, 2B_o and 3B_o, we show that accurate exchange values can be obtained even in cases where exchange rates exceed 10,000 s^?1. The utility of the double quantum experiment is demonstrated with a pair of cavity mutants of T4 lysozyme (T4L) with ground and excited states interchanged and with exchange rates differing by fourfold (~?900 s^?1 and ~?3600 s^?1), as well as with a fast-folding domain where the unfolded state lifetime is ~?80 µs.     

Kidney Transplantation from Pediatric Donors in a Single Chinese Center

To report clinical outcomes of kidney transplantation from pediatric brain and cardiac death donors (DBCD) in a single Chinese center and to investigate its feasibility to expand organ donor pool. 18 recipients, transplanted between August 2011 and October 2013 in the First Affiliated Hospital of Zhengzhou University, receive a single graft from DBCD donors age ranged from 1.5 to 13 years old. Renal function expressed as serum creatinine, blood urea nitrogen as well as eGFR values at 1, 2 weeks as well as 1-, 3-, 6-, and 12-months post-transplantation was evaluated. Graft size was also monitored at the same time by ultrasonography. In addition, delayed graft function, acute rejection, surgical complication as well as patient and graft survival were also assessed. The primary causes of DBCD donors included six cases of severe brain trauma and three cases of cerebral hemorrhage. The mean age of DBCD donors was (7.2 ± 3.4) years (range 1.5–13). The mean weight of DBCD donors was (29.8 ± 15.3) kilogram (range 13–67). The mean height of DBCD donors was (118.3 ± 27.8) centimeter (range 70–173). ECMO was applied to DBCD donors to avoid warm ischemia time and the applicating time was (79.8 ± 44.5) (range 32–180) minutes.There were seven males and 11 females recipients. Among which, 16 recipients were pediatrics and two recipients were adults. The mean age of the recipients was (14.6 ± 9.7) years (range 4–47). The mean weight of recipients was (31.9 ± 12.4) kilogram (range 11–54). The mean height of recipients was (138.0 ± 23.7) centimeter (range 84–172). Renal function recovered to normal within the first-week post-operation except one recipient which occurred acute rejection. Two cases of renal artery stenosis were found 2-week and 3-month post-transplantation, respectively. They subsequently underwent ballon angioplasty and followed up for 8 and 12 months, respectively, and no recurrence was found. One recipient developed ureteral leak. Five weeks later, the ureter leak healed after adequate drainage and prolongation of indwelling catheter. Graft size significantly and continuously increased during the first year, especially in the first 3-month post-transplantation. All the 18 recipients are alive at the last follow-up. Among which, 16 recipients are followed up for 12 months and 1-year recipient/graft survival rate is 100 %. The use of single kidney graft from pediatric DBCD could yield good short-term results.     

Characteristics Of Patients With Ketosis-Prone Diabetes (Kpd) Presenting With Acute Pancreatitis: Implications For The Natural History And Etiology Of A Kpd Subgroup

ObjectiveReports of concomitant diabetic ketoacidosis (DKA) and acute pancreatitis (AP) are lacking among emerging forms of diabetes. This longitudinal study characterized ketosis-prone diabetes (KPD) in patients presenting with concomitant AP and DKA.MethodsMulti-ethnic KPD patients (N = 755) were followed prospectively for 1 year from the time of index DKA using repeated metabolic and beta cell functional reserve measures. Baseline and longitudinal characteristics were compared between KPD patients whose index DKA was associated with (n = 54) or without (n = 701) AP.ResultsThe AP group had significantly higher baseline serum amylase, lipase, and triglyceride levels and significantly lower bicarbonate levels than the non-AP group. AP patients had significantly greater C-peptide area-under-the-curve with glucagon stimulation shortly after the index DKA, and higher fasting C-peptide (FCP) levels 6 to 12 months later. Using the validated "Aβ" KPD classification, 85% of AP patients had β+ status (preserved beta cell functional reserve), compared to 60% of non-AP patients (P = .04). Multivariate analysis revealed that among the β+ KPD subgroup with an identifiable precipitating factor for DKA ("provoked" DKA), patients with AP had worse long-term glycemic outcomes than patients whose DKA was associated with other factors.ConclusionDespite greater clinical severity at presentation, KPD patients with AP have better preserved beta cell function than those without AP. β+ KPD patients presenting with AP have worse long-term glycemic control than those with other causes of provoked DKA. Factors other than beta cell function negatively impact glycemic control in KPD patients presenting with AP.