A theoretical equation has been developed to described the rate of slow crack growth in an ethylene‐hexene copolymer in terms of the basic morphological parameters. These parameters are spacing of the butyl branches, number of tie molecules, and the thickness of the lamellar crystal. Experimentally, the thickness of the lamellae and the long period were determined as functions of the branch density. The calculation of the number of tie molecules is based on the values of the molecular weight and the long period. The model of slow crack growth is based on the rate of disentanglement of the tie molecules. The rate of disentanglement varies inversely with the number of tie molecules and directly with the number of tie molecules that are not pinned by the branches.
An experiment was conducted to estimate relative bioavailability of Zn in 3 organic zinc sources with different chelation strength (Q(f)) compared with ZnSO(4). A total of 1,092, 1-d-old male broiler chicks were assigned randomly to 6 replicate cages (14 chicks per cage) for each of 13 treatments. Dietary treatments included the basal corn-soybean meal diet (27.82 mg of Zn/kg of DM) supplemented with 0, 30, 60, or 90 mg of added Zn as reagent ZnSO(4), or Zn sources with Q(f) of 6.5 (11.93% Zn; Zn AA C), 30.7 (13.27% Zn; Zn Pro B), or 944.0 (18.61% Zn; Zn Pro A)/kg, which are considered as weak, moderate, or strong Q(f), respectively. Bone Zn, pancreas Zn, pancreas metallothionein (MT) concentration, and pancreas MT messenger RNA (mRNA) were analyzed at 6, 10, or 14 d of age. The results showed that bone Zn, pancreas Zn, pancreas MT concentration, and pancreas MT mRNA increased linearly (P < 0.001) as dietary Zn concentration increased at all ages. At 6 d of age, pancreas MT mRNA differed (P < 0.001) among dietary Zn sources, and the same tendency was observed at 10 (P = 0.08) or 14 d (P = 0.06) of age. The R(2) for a linear model was greater on d 6 than d 10 or 14 for all the response criteria. Based on slope ratios from the multiple linear regression of pancreas MT mRNA concentration on daily intake of dietary Zn, the bioavailability of Zn AA C, Zn Pro B, and Zn Pro A relative to ZnSO(4) (100%) were 100.0, 121.1, and 72.3%, respectively, at 6 d of age. The results indicated that MT mRNA concentration in pancreas was more sensitive in reflecting differences in bioavailability among organic Zn sources than the MT concentration in pancreas or other indices. Moreover, the bioavailability of organic Zn sources was closely related to their Q(f).
To identify novel targets for neuropathic pain, 3097 mouse knockout lines were tested in acute and persistent pain behavior assays. One of the lines from this screen, which contained a null allele of the adapter protein-2 associated kinase 1 (AAK1) gene, had a normal response in acute pain assays (hot plate, phase I formalin), but a markedly reduced response to persistent pain in phase II formalin. AAK1 knockout mice also failed to develop tactile allodynia following the Chung procedure of spinal nerve ligation (SNL). Based on these findings, potent, small-molecule inhibitors of AAK1 were identified. Studies in mice showed that one such inhibitor, LP-935509, caused a reduced pain response in phase II formalin and reversed fully established pain behavior following the SNL procedure. Further studies showed that the inhibitor also reduced evoked pain responses in the rat chronic constriction injury (CCI) model and the rat streptozotocin model of diabetic peripheral neuropathy. Using a nonbrain-penetrant AAK1 inhibitor and local administration of an AAK1 inhibitor, the relevant pool of AAK1 for antineuropathic action was found to be in the spinal cord. Consistent with these results, AAK1 inhibitors dose-dependently reduced the increased spontaneous neural activity in the spinal cord caused by CCI and blocked the development of windup induced by repeated electrical stimulation of the paw. The mechanism of AAK1 antinociception was further investigated with inhibitors of α2 adrenergic and opioid receptors. These studies showed that α2 adrenergic receptor inhibitors, but not opioid receptor inhibitors, not only prevented AAK1 inhibitor antineuropathic action in behavioral assays, but also blocked the AAK1 inhibitor–induced reduction in spinal neural activity in the rat CCI model. Hence, AAK1 inhibitors are a novel therapeutic approach to neuropathic pain with activity in animal models that is mechanistically linked (behaviorally and electrophysiologically) to α2 adrenergic signaling, a pathway known to be antinociceptive in humans.
An experiment was conducted to estimate the optimal dietary zinc level for broiler chicks fed a corn-soybean meal diet. A total of 384 one-day-old male broiler chicks were assigned randomly to dietary treatments for 21 d. These treatments included a basal corn-soybean meal diet (28.32 mg of Zn/kg) supplemented with 0, 20, 40, 60, 80, 100, 120, or 140 mg of Zn/kg in the form of reagent-grade ZnSO(4).7H(2)O. All treatments were replicated 6 times using 8 chicks per pen. Tissue Zn concentration, Zn metalloenzyme activity, metallothionein (MT) concentration, MT mRNA level, and Zn transporter-2 (ZnT-2) mRNA level were analyzed for choosing suitable criterion to determine the optimal dietary Zn level for broilers. Regression analysis was performed to estimate optimal dietary Zn level in the presence of quadratic or asymptotic responses. Results showed that weight gain and feed intake were increased with dietary Zn level (P < 0.05), and the maximum weight gain and feed intake were observed in the diet supplemented with 20 mg of Zn/kg (48.37 mg/kg, total dietary Zn). Pancreas MT and MT mRNA increased linearly with Zn supplementation. According to the asymptotic model, the optimal Zn requirement of chicks from hatch to 21 d of age was 59.15 mg/kg for pancreas Zn and 61.70 mg/kg for bone Zn respectively. Quadratic responses were exhibited by serum 5'-nucleotidase activity and pancreas Zn transporter-2 mRNA level, resulting in total optimal dietary levels of 80.50 and 84.09 mg/kg, respectively. Based on results from this study, the optimal dietary Zn level of chicks from hatch to 21 d of age is 84 mg/kg.
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