Search

Rapeseed (RS) is an abundant and inexpensive source of energy and AA in diets for monogastrics and a sustainable alternative to soybean meal. It also contains diverse bioactive phytochemicals that could have antinutritional effects at high dose. When the RS-derived feed ingredients (RSF) are used in swine diets, the uptake of these nutrients and phytochemicals is expected to affect the metabolic system. In this study, 2 groups of young pigs (17.8 ± 2.7 kg initial BW) were equally fed a soybean meal-based control diet and an RSF-based diet, respectively, for 3 wk. Digesta, liver, and serum samples from these pigs were examined by liquid chromatography–mass spectrometry–based metabolomic analysis to determine the metabolic effects of the 2 diets. Analyses of digesta samples revealed that sinapine, sinapic acid, and gluconapin were robust exposure markers of RS. The distribution of free AA along the intestine of RSF pigs was consistent with the reduced apparent ileal digestibility of AA observed in these pigs. Despite its higher fiber content, the RSF diet did not affect microbial metabolites in the digesta, including short-chain fatty acids and secondary bile acids. Analyses of the liver and serum samples revealed that RSF altered the levels of AA metabolites involved in the urea cycle and 1-carbon metabolism. More importantly, RSF increased the levels of multiple oxidized metabolites and aldehydes while decreased the levels of ascorbic acid and docosahexaenoic acid–containing lipids in the liver and serum, suggesting that RSF could disrupt redox balance in young pigs. Overall, the results indicated that RSF elicited diverse metabolic events in young pigs through its influences on nutrient and antioxidant metabolism, which might affect the performance and health in long-term feeding and also provide the venues for nutritional and processing interventions to improve the utilization of RSF in pigs.

The emergence of skin‐containing vascularized composite allografts (VCAs) has provided impetus to understand factors affecting rejection and tolerance of skin. VCAtolerance can be established in miniature swine across haploidentical MHCbarriers using mixed chimerism. Because the deceased donor pool for VCAs does not permit MHCantigen matching, clinical VCAs are transplanted across varying MHCdisparities. We investigated whether sharing of MHCclass I or IIantigens between donors and recipients influences VCAskin tolerance. Miniature swine were conditioned nonmyeloablatively and received hematopoietic stem cell transplants and VCAs across MHCclass I (n = 3) or class II(n = 3) barriers. In vitroimmune responsiveness was assessed, and VCAskin‐resident leukocytes were characterized by flow cytometry. Stable mixed chimerism was established in all animals. MHCclass II–mismatched chimeras were tolerant of VCAs. MHCclass I–mismatched animals, however, rejected VCAskin, characterized by infiltration of recipient‐type CD8+lymphocytes. Systemic donor‐specific nonresponsiveness was maintained, including after VCArejection. This study shows that MHCantigen matching influences VCAskin rejection and suggests that local regulation of immune tolerance is critical in long‐term acceptance of all VCAcomponents. These results help elucidate novel mechanisms underlying skin tolerance and identify clinically relevant VCAtolerance strategies. The specificity of MHC antigen matching between donors and recipients determines skin tolerance in vascularized composite allografts in a mixed chimerism‐based miniature swine model.

AbstractIn industrialised areas, teleost fish are often exposed to anthropogenic changes of the water quality. These often have negative effects on species with a narrow ecological range. Species with a wider ecological range, such as the three-spined stickleback (Gasterosteus aculeatusLinneaus, 1758), might benefit if water quality alteration reduces interspecific competition and/or parasite infection pressure. In the present study, we investigated sticklebacks in an inland brook, in which the inlet of warm and salty coal mine drainage water increases water temperature and changes the brook from freshwater to brackish (approx. 20 mS cm−1) conditions. We collected sticklebacks up- and downstream of the saltwater inlet (henceforth called freshwater and saltwater sites or habitats) in monthly intervals from April to October 2010, and monitored their body condition parameters and parasite infections. In particular during spring, the water temperature was higher (3.7–4.5°C) in the saltwater habitat and juvenile sticklebacks occurred earlier and grew faster compared to juveniles in the freshwater habitat. In the saltwater habitat, fewer parasite species were detected compared to the freshwater situation (7 vs. 10). Moreover, parasite index, which peaked in young-of-the-year sticklebacks in September, was lower in sticklebacks from the saltwater site. The present study suggests that changes of freshwater conditions by the inlet of warm and salty coal mine drainage water match the adaptive range of three-spined sticklebacks, which grew faster and had lower parasite burden in the altered habitat.

Oxidative degradation by reactive oxygen species (ROS) from inflammation initiates cross-linking, depolymerization, and formation of a quasi-crystalline quality in polypropylene (PP) meshes that cause embrittlement (J Urol 188:1052, 2012). Embrittlement leads to change in tensile strength and is associated with post-operative complications that include pain, adhesion, dislodgment, and fragmentation. A laboratory environment was constructed to study the relationship between concentration of ROS and change in tensile strength. Samples of Ethicon Ultrapro© PP mesh were exposed to 1 mM, 0.1 M, or 1 M hydrogen peroxide solutions for 6 months and were subjected to load displacement tensile testing (LDTT) and compared to unexposed (0 M) meshes of the same brand. Load at failure and elongation to failure after LDTT were determined with 95 % confidence interval. For unexposed (0 M) samples, tensile strength was 28.0 ± 2.4 lbf and elongation to failure was 2.0 ± 0.3 in. For samples exposed to 1 mM, tensile strength was 19.2 ± 1.1 lbf and the elongation to failure was 2.0 ± 0.1 in. For samples exposed to 0.1 M, tensile strength was 19.3 ± 1.6 lbf and elongation to failure was 1.9 ± 0.1 in. For samples exposed to 1 M, tensile strength was 20.7 ± 1.2 lbf and elongation to failure was 0.47 ± 0.02 in. The results demonstrated that a 6-month exposure to a physiologic range of ROS (1 mM) decreased tensile strength of PP mesh by 31 %. 1 mM and 0.1 M samples behaved similarly demonstrating properties of a quasi-crystalline nature. 1 M samples displayed qualities of extreme embrittlement. Scanning electron microscopy (SEM) observed fiber changes. 1 M meshes had features of brittle materials. Knowledge of changes in physical properties of PP meshes is useful for considerations for the development of a more biocompatible surgical mesh.

Kidney‐induced cardiac allograft tolerance requires MHC‐matching between kidney allograft parenchyma and heart allografts, suggesting that cells intrinsic to the kidney enable cardiac allograft tolerance.

Mixed chimerism approaches for induction of tolerance of solid organ transplants have been applied successfully in animal models and in the clinic. However, in xenogeneic models (pig-to-primate), host macrophages participate in the rapid clearance of porcine hematopoietic progenitor cells, hindering the ability to achieve mixed chimerism. CD47 is a cell-surface molecule that interacts in a species-specific manner with SIRPα receptors on macrophages to inhibit phagocytosis and expression of human CD47 (hCD47) on porcine cells has been shown to inhibit phagocytosis by primate macrophages. We report here the generation of hCD47 transgenic GalT-KO miniature swine that express hCD47 in all blood cell lineages. The effect of hCD47 expression on xenogeneic hematopoietic engraftment was tested in an in vivomouse model of human hematopoietic cell engraftment. High-level porcine chimerism was observed in the bone marrow of hCD47 progenitor cell recipients and smaller but readily measurable chimerism levels were observed in the peripheral blood of these recipients. In contrast, transplantation of WT progenitor cells resulted in little or no bone marrow engraftment and no detectable peripheral chimerism. These results demonstrate a substantial protective effect of hCD47 expression on engraftment and persistence of porcine cells in this model, presumably by modulation of macrophage phagocytosis.

Establishment of stable mixed chimerism across MHC barriers in a clinically relevant miniature swine model induces tolerance of all components of vascularized composite allografts including the critical and challenging skin component.

Liquid hydrogen has historically been limited in proximity to baseload liquefiers and research laboratories. This accessibility barrier is a primary limitation to the development of advanced aircraft and is exacerbated by recent trends in unmanned aerial systems to convert to electric propulsion systems. This article describes the design, construction, and commissioning of a self-contained, automated, and deployable liquid hydrogen production and fueling system. Housed within a mil-spec shipping container, the system utilizes a water purifier, proton exchange membrane electrolyzer, cryogenic refrigerator, and custom liquid hydrogen dewar. The system requires only water, electricity, and periodic helium purge gas input for continuous operation. Overall system performance specifications are provided. The system demonstrates the capability of field deployable hydrogen liquefiers and fueling systems.

En dépit d’un bilan d’imagerie exhaustif, les lésions tumorales endocrines primitives restent fréquemment inconnues. Leur connaissance permet d’adapter la stratégie thérapeutique, mais surtout d’envisager une exérèse chirurgicale curative.

AbstractThis article examines the impact of international law on the ability of States to mitigate the effects of financial crises. It focuses on the invocation of investment treaty disciplines in the aftermath of the 2001?2002 Argentine financial crisis, and the adjudication of Argentina's defence of a state of necessity under both subject treaties and at customary international law. The article uncovers three interpretative methods in the jurisprudence on the relationship between the treaty exception and customary plea of necessity: methodologies I (confluence), II (lex specialis) and III (primary-secondary applications). Method I is the dominant approach in the jurisprudence and the most restrictive of the three readings. The article argues that method I is mistaken both on a careful interpretation of the two legal standards and on a broader historical analysis of the emergence of investment treaty norms. Given these substantive flaws, the article isolates the motivations to account for the popularity of this method through a close reading of the awards. These reveal continuing tensions in the field, not least the problematic suggestion that a single value of protection should exclusively inform our understanding of the purpose of investment treaties. These sociological features of investor?State arbitration should, it is suggested, inform our choice on other interpretative methods. This comes down to an election between methods II (lex specialis) and III (primary?secondary applications). Method III is the most convincing and coherent reading of the relationship between the two legal standards. The article concludes by offering a framework to address the key interpretative questions implicated in that method: (a) the identification and scope of the notion of ?public order? and a State's ?essential security interests?; and (b) the appropriate test of ?necessity? or means?end scrutiny.

Induction of mixed allogeneic chimerism is a promising approach for achieving donor‐specific tolerance, thereby obviating the need for life‐long immunosuppression for solid organ allograft acceptance. In mice receiving a low dose (3Gy) of total body irradiation, allogeneic bone marrow transplantation combined with anti‐CD154 tolerizes peripheral CD4 and CD8 T cells, allowing achievement of mixed chimerism with specific tolerance to donor. With this approach, peripheral CD8 T‐cell tolerance requires recipient MHC class II, CD4 T cells, B cells and DCs. Recipient‐type B cells from chimeras that were tolerant to donor still promoted CD8 T‐cell tolerance, but their role could not be replaced by donor‐type B cells. Using recipients whose B cells or DCs specifically lack MHC class I and/or class II or lack CD80 and CD86, we demonstrate that dendritic cells (DCs) must express CD80/86 and either MHC class I or class II to promote CD8 tolerance. In contrast, B cells, though required, did not need to express MHC class I or class II or CD80/86 to promote CD8 tolerance. Moreover, recipient IDO and IL‐10 were not required. Thus, antigen presentation by recipient DCs and not by B cells is critical for peripheral alloreactive CD8 T cell tolerance.

We improve the performance of the Perfectly Matched Layer (PML) by using an automatic hp‐adaptive discretization. By means of hp‐adaptivity, we obtain a sequence of discrete solutions that converges exponentially to the continuum solution. Asymptotically, we thus recover the property of the PML of having a zero reflection coefficient for all angles of incidence and all frequencies on the continuum level. This allows us to minimize the reflections from the discrete PML to an arbitrary level of accuracy while retaining optimal computational efficiency. Since our hp‐adaptive scheme is automatic, no interaction with the user is required. This renders tedious parameter tuning of the PML obsolete. We demonstrate the improvement of the PML performance by hp‐adaptivity through numerical results for acoustic, elastodynamic, and electromagnetic wave‐propagation problems in the frequency domain and in different systems of coordinates. © 2007 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq 23: 832–858, 2007

Abstract: In this study, we investigated predictors of utilization of physician, hospital, and emergency room services in a sample of 277 elderly patients during the first year following a diagnosis of lung cancer. Data were obtained by a combination of patient interview and patient self-administered questionnaire at four intervals: baseline (wave 1), 3 months (wave 2), 6 months (wave 3), and 12 months (wave 4). Of the 277 patients, 242 provided data at wave 1, 209 at wave 2, 157 at wave 3, and 115 at wave 4. Symptomatology was assessed with the Symptom Experience Scale (simple count of symptoms present, chosen from a list of 37 cancer-related symptoms), and physical functioning was assessed with the Medical Outcomes Study 36-Item Short Form Health Survey. Analysis of covariance models were implemented separately for the active treatment period (0–6 months) and the continuing care period (6–12 months) to determine how age, gender, comorbidity, length of survival, treatment status, stage of disease, cancer site, physical functioning, and symptom count were related to physician visits, nights in hospital, and emergency room visits. During the active treatment period, patients with worse physical functioning reported more hospital nights (p=0.002) and more emergency room visits (p=0.013), while men reported more frequent emergency room visits (p=0.032) and more nights in hospital (p=0.006) than women. Patients reporting more symptoms also reported more physician visits (p=0.020). During the continuing care period, physical functioning had a similar relation to hospital nights (p=0.005) and emergency room visits (p=0.003), and patients with late-stage disease reported more physician visits than patients with early-stage disease (p=0.003).

We investigated population differences in immunological adaptation of three-spined sticklebacks (Gasterosteus aculeatus) to one of their most abundant macroparasites, the eye fluke Diplostomum pseudospathaceum. We compared infection success in lab-bred fish of 2 populations in northern Germany, from a lake, where eye flukes are prevalent, and a river, where these parasites do not occur. In order to discriminate between protection through innate and acquired immunity, we exposed fish either only once or repeatedly. Lake fish were significantly less susceptible than river sticklebacks already after a single exposure, indicating that in sympatric hosts innate immunity plays the major role in the defence against this helminth infection. In both habitat types, previous exposures only marginally decreased infection rates within 12 weeks. Lake fish showed higher immunocompentence by means of respiratory burst activity and spleen size, regardless of the infection status. Furthermore, they were in a better energy status than river fish, as indicated by a higher hepatosomatic index and haematocrit value. Interestingly, F1 hybrid fish of both populations ranged between the pure habitat types in parasite susceptibility as well as in immunological and condition parameters. Our results suggest that sticklebacks from lakes are better adapted to cope with higher parasite abundance in this habitat.

With the recent sequencing of its entire genome, the yeast Saccharomyces cerevisiae has gained considerable interest in the field of anticancer research. The genetic properties of the yeast allow easy selection of a variety of mutants, as their related phenotypes provide valuable information on anticancer drugs effects in vivo. Moreover, the yeast has been extensively studied as a model system to decipher basic cellular processes that are well conserved from yeast to human and implicated in cancer establishment and progression. We discuss the advantages of Saccharomyces cerevisiae for investigating the metabolism of pyrimidines, a major target for anticancer chemotherapy. We also emphasize the links between basic science in the pyrimidine metabolism and new anticancer antimetabolites as well as future prospects in this field.

Colorectal cancer constitutes a major health problem for elderly patients. The disease and its stage, treatment, and attendant symptoms can have significant negative impact on the mental functioning of these patients. As part of a larger longitudinal study, 158 patients 65 years of age or older with an incident diagnosis of colorectal cancer were recruited from 23 sites within a Midwestern state. Random effects regression analysis techniques were used to analyze how age, gender, race, presence of a family caregiver, co-morbid conditions, stage of disease at diagnosis, and the time-dependent variables marital status, employment status, symptoms, physical functioning, social functioning, and treatment predict depressive symptomatology at four assessments over the 1st year following diagnosis. Gender, race, co-morbid conditions, physical functioning, social functioning, and symptoms were significant predictors of depressive symptomatology over the four waves of the study. Female patients, African Americans, and patients with two or more co-morbid conditions exhibited more depressive symptomatology. Both more symptoms and more restricted physical and social functioning corresponded to higher levels of depressive symptomatology. At a clinical level of patient care, these findings mandate early identification of psychosocial difficulties experienced, an individualized symptom management plan and the application of other interventions, such as information giving, reassurance and referral to other resources, with particular attention to African American and female patients.

The outcome of a parasite infection is the result of the interaction between the host and the parasite. In the system we studied, there are 3 critical stages for the outcome of infection of the (intermediate) host, the copepod Macrocyclops albidus, with the cestode Schistocephalus solidus. During the establishment phase of the parasite, the host may firstly avoid ingesting the parasite and, secondly, may prevent the parasite from entering the body cavity and, thirdly, during the growth phase of the parasite, the host's immune system may eliminate the parasite from the body cavity. We were able to study the growth phase separately from the establishment phase. The establishment phase was influenced by characteristics of the host as well as characteristics of the parasites. Small copepods and males performed poorly; they were more often infected and had a lower survival. Parasites from different sib-groups differed in infectivity. During the growth phase some disappearance of parasites was observed. However, this could not be related to any of the studied characteristics of the host, and the sib-groups of parasites did not seem to differ in their likelihood to disappear. Instead, we suggest that disappearance of parasites, once they have entered the body cavity, may be due to intrinsic mortality of the parasites, independent of the host or the sib-group that the parasites belong to. This indicates that the crucial interactions between host and parasite determining the outcome of infection takes place in the short time-period between ingestion and penetration of the gut-wall.

We have previously shown that high levels of multilineage mixed hematopoietic chimerism and systemic T-cell tolerance can be achieved in mice without myeloablation through the use of anti-CD40L and costimulatory blockade alone (plus CTLA4Ig) or with recipient CD8 depletion and allogeneic bone marrow transplantation. Chimeric mice permanently accept donor skin grafts (> 100 days), and rapidly reject third-party grafts. The mechanisms by which costimulatory blockade facilitates the engraftment of allogeneic hematopoietic cells have not been defined. To further understand the in vivo mechanisms by which the administration of anti-CD40L mAb facilitates the engraftment of donor bone marrow and rapidly tolerizes CD4⁺ T cells, we analyzed the establishment of chimerism and tolerance in CD40L^-/- mice. We demonstrate here that anti-CD40L mAb treatment is required only to prevent CD40L/CD40 interactions, and that no signal to the T cell through CD40L is necessary for the induction of CD4⁺ tolerance. Peripheral deletion of donor-reactive CD4⁺ T cells occurs rapidly in CD40L^-/- mice receiving bone marrow transplantation (BMT), indicating that this deletion in the presence of anti-CD40L is not due to targeting of activated CD4⁺ cells by the antibody. Complete CD4⁺ cell tolerance is observed by both skin graft acceptance and in vitro assays before deletion is complete, indicating that additional mechanisms play a role in inducing CD4⁺ T-cell tolerance as the result of BMT in the presence of CD40/CD40L blockade.

Drug‐induced agranulocytosis (DIA) is often caused by antithyroid drugs. We retrospectively studied the use of granulocyte colony‐stimulating factor (G‐CSF) therapy in antithyroid‐DIA. Data for 20 patients (10 treated with G‐CSF) with antithyroid‐DIA (neutrophil count <0.5×109/l) were extracted from a cohort study of DIA patients (n=110). G‐CSF (300 μg/day subcutaneously) was used where the neutrophil count was <0.1×109/l, or the patient was aged >70 years, or there were severe features of infection or underlying disease. Mean patient age was 62 years (range 34–87); sex ratio (M/F) was 0.05. Carbimazole (n=19) and benzylthiouracile (n=1) were the causative drugs, at mean doses of 30 mg/day (range 20–60) and 100 mg/day (range 50–150), respectively, for a mean of 37 days (range 31–90). Antithyroid drugs were prescribed for Graves' disease (n=8), thyrotoxicosis related to amiodarone intake (n=6) and multinodular goitre (n=6). Clinical features included isolated fever (n=7), pneumonia (n=5), septicaemia or septic shock (n=5) and acute tonsillitis (n=3). Mean neutrophil count was 0.07±0.1×109/l. No patient died. Mean durations of haematological recovery, antibiotic therapy and hospitalization were significantly reduced with G‐CSF: 6.8±4 days vs. 11.6±5; 7.5±3.8 days vs. 12±4.5; and 7.3±4.8 days vs. 13±6.1, respectively (all p<0.05). G‐CSF induced flu‐like symptoms in 30% of patients, but reduced overall costs.

Abstract:  This study investigated how treatment options, symptom severity, prediagnosis levels of physical functioning, comorbidity, gender, and age predicted current physical functioning in geriatric patients with small-cell or non-small-cell lung cancer, 12 weeks after their diagnosis. The study involved 146 patients aged 65 years and over with an incident diagnosis of lung cancer. Analysis of covariance revealed no significant differences in physical functioning according to treatment type, small-cell versus non-small-cell classification or gender. Significant predictors of current physical functioning were symptom severity and prior physical functioning. The characteristics of a high-risk profile for disruption in physical functioning of elderly lung cancer patients 12 weeks after their diagnosis would include pre-existing physical impairment and high levels of symptomatology.

Abstract: Cytidine metabolism in the yeast Saccharomyces cerevisiae was analyzed by genetic and biochemical approaches. Disruption of a unique ORF (Genbank accession No. U 20865) bearing homology with eucaryotic or bacterial cytidine deaminases abolished cytidine deaminase activity and resulted in 5-fluorocytidine resistance. The gene encoding cytidine deaminase will be referred to as CDD1 (Genbank accession number AF080089). The ability to isolate mutants resistant to 5-fluorocytidine which mapped to five other loci demonstrated the existence of a complex cytidine metabolic network. Deciphering this network revealed several original features: (1) cytidine entry is mediated by the purine-cytosine transporter (Fcy2p),(2) cytidine is cleaved into cytosine by the uridine nucleosidase (Urh1p),(3) cytidine is phosphorylated into CMP by the uridine kinase (Urk1p),(4) a block in cytosine deaminase (Fcy1p), but not in cytidine deaminase (Cdd1p), constitutes a limiting step in cytidine utilisation as a UMP precursor.

As a special version of the good-genes hypothesis, it was recently proposed that females could benefit from choosing drive-resistant males in a meiotic drive system. Here, we examine with a three-locus, six-allele population genetic model whether female choice for drive resistance can evolve. An allele leading to female preference for drive-resistant males was introduced at low frequency into a population polymorphic for meiotic drive and drive resistance. Our simulations show that female choice of drive-resistant males is disadvantageous when resistance is Y-linked. This disadvantage occurs because, at equilibrium, drive-resistant males have lower reproductive success than drive-susceptible males. Thus, female choice of drive-susceptible males can evolve when resistance is Y-linked. When resistance is autosomal, selection on female choice for drive resistance is less strong and depends on the frequency of choice: female preference of resistant males is favoured when choice is rare and disadvantageous when choice is frequent, leading to a stable equilibrium at a low frequency of the choice allele. Independent of the location of drive resistance alleles, males with the non-driving allele always have above average reproductive success. Female choice is therefore beneficial when choosy females prefer males with the non-driving allele.

The second order Møller-Plesset (MP2) perturbation treatment with the 6-31G* basis set was applied to the cyclic structure of C8. It has been found that its minimum energy structure is nonplanar, possessing D2d point symmetry. The nonplanar species is located about 56 kJ mol-1 below a planar cyclic stationary point. The latter structure has C4h symmetry and exhibits two imaginary vibrational frequencies. This finding reveals a distinct difference in the potential hypersurface topology resulting from the correlated MP2 and SCF approaches (as in the SCF/6-31G* treatment the C4h species is a local energy minimum). The MP2/6-31G* geometry, energy, and harmonic vibrational characteristics are reported.

The combustion of pure iron rods in oxygen is characterized by excess oxygen in the molten products. The amount of oxygen dissolved in the molten mass exceeds that required for stoichiometric haematite, Fe2O3, the highest oxidation state for solid iron oxide. Oxygen mass-balance calculations and post-test product analysis suggest that the average oxygen-to-iron molar ratio of the molten oxide product is as high as 2.1 and possibly higher. This corresponds to an increase in oxygen solubility in the molten iron oxide (over that of molten iron metal), which is compatible with the existence of various forms of ferrite ions such as FeO2−1, Fe2O5−4, FeO3−3, and Fe2O7−8. The presence of this excess oxygen confirms the proposed heterogeneous mechanism for the burning of iron, that is, that primary oxidation takes place at an interface between liquid iron and the molten combustion products containing the excess oxygen.