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Researchers have been aiming to replace copper with carbon nanotube/copper nanocomposites, which are lighter and exhibit better electrical, mechanical, and thermal properties. However, the strength is far below pure carbon nanotube assembly and even much lower than some copper-based alloys. This disadvantage hinders the extensive application of carbon nanotube/copper nanocomposites. In this study, the carbon nanotube/aluminum–copper nanocomposites with ultra-strength and stiffness were prepared. The strength and elasticity modulus of composite reached as high as 6.6 and 500 GPa, respectively, while a high conductivity of 1.8 × 107S/m was maintained. This can be attributed to the diffusion of Cu and Al atoms into the carbon nanotube fiber, which enhances friction between the carbon nanotubes by “pinning” and “bridging”. This structure provides us with novel insights into the design of carbon nanotubes/metal nanocomposites with ultrahigh strength and conductivity.

Let-7 miRNAs are involved in carcinogenesis and tumor progression through their roles in maintaining differentiation and normal development. However, there is little research focusing on the effects of let-7 on Wnt-activated self-renewal of breast cancer stem cells. By analyzing the expression levels of let-7 family members in clinical tissues, we found that higher expression levels of let-7b and let-7c were correlated with better clinical prognosis of patients with estrogen receptor (ER)a-positive breast tumor. Further, we found that only let-7c was inversely correlated with ERa expression, and there is corelationship between let-7c and Wnt signaling in clinical tissues. Aldehyde dehydrogenase (ALDH)1 sorting and mammosphere formation assays showed that let-7c inhibited the self-renewal of stem cells in ERa-positive breast cancer. Let-7c decreased ERa expression through directly binding to the 3’UTR (untranslated region), and let-7c inhibited the estrogen-induced activation of Wnt signaling. Depletion of ERa abolished let-7c functions in stem cell signatures, which further confirmed that let-7c inhibited estrogen-induced Wnt activity through decreasing ERa expression. Taken together, our findings identified a biochemical and functional link between let-7c with ERa/Wnt signaling in breast cancer stem cells.

Background:: Obesity and insulin resistance lead to islet hyperplasia. However, how the islet remodeling influences the pancreatic environment and the associated neurovascular networks is largely unknown. The lack of information is primarily due to the difficulty of global visualization of the hyperplasic islet (>200?µm) and the neurovascular environment with high definition. Methods:: We modulated the pancreatic optical property to achieve 3-dimensional (3-D) whole-islet histology and to integrate transmitted light microscopy (which provides the ground-truth tissue information) with confocal fluorescence imaging. The new optical and imaging conditions were used to globally examine the hyperplastic islets of the young (2 months) obese db/db and ob/ob mice, which otherwise cannot be easily portrayed by the standard microtome-based histology. The voxel-based islet micrographs were digitally processed for stereo projection and qualitative and quantitative analyses of the islet tissue networks. Results:: Paired staining and imaging of the pancreatic islets, ducts and neurovascular networks reveal the unexpected formation of the ‘neuro-insular-ductal complex’ in the young obese mice. The complex consists of the peri- and/or intra-islet ducts and prominent peri-ductal sympathetic nerves; the latter contributes to a marked increase in islet sympathetic innervation. In vascular characterization, we identify a decreased perivascular density of the ob/ob islet pericytes, which adapt to ensheathing the dilated microvessels with hypertrophic processes. Conclusions:: Modulation of pancreatic optical property enables 3-D panoramic examination of islets in the young hyperphagic mice to reveal the formation of the islet–duct complex and neurovascular remodeling. On the basis of the morphological proximity of the remodeled tissue networks, we propose a reactive islet microenvironment consisting of the endocrine cells, ductal epithelium and neurovascular tissues in response to the metabolic challenge that is experienced early in life.

Inefficient release of polymer/DNA complexes from endocytic vesicles into the cytoplasm and the cytotoxic nature of cationic polymers are two of the primary causes of poor gene delivery. EG−polyurethane [poly(ethylene glycol)−PU, Poly 1], EGDM−polyurethane [poly(ethylene glycol), 2-(dimethylamino)ethylamine−PU, Poly 2], and MDEADM−polyurethane [N-methyldiethanolamine, 2-(dimethylamino)ethylamine−PU, Poly 3] were designed in this study to overcome these obstacles. The structural characteristics of polyurethanes and physicochemical properties of their formed complexes with DNA were determined to correlate their transfection efficiency. The results revealed that Poly 2 and Poly 3 could bind with plasmid DNA and yield positively charged complexes with a size required for transfection. Poly 3 showed the best in buffering capacity and its formed complexes with DNA could transfect COS-7 cells better than those of Poly 2 and Poly 1. This study reveals that the amine groups in the polymeric structure and the buffer capacity of a polymeric transfectant would affect its potential in DNA delivery. Also the size and binding properties of DNA and polymeric transfectants can be in correlation to the transfection efficiency of resulting DNA/polymer complexes.

Some FeTPP−Cl/carbon electrocatalysts, heat-treated at temperatures up to 800 °C, have been studied with cyclic voltammetry, x-ray photoelectron spectroscopy, extended X-ray absorption fine structure, and in situ Mössbauer spectroscopy. It appears that the heat treatment induces considerable site heterogeneity in electronic terms, although structurally the Fe−N4 moiety seems persistent. The data indicate that only part of these Fe−N4 sites contributes to the activity for the electrochemical reduction of O2 but that they operate according to the well-known redox mechanism.

Abstract: Sanguinarine, a benzophenanthridine alkaloid, has anticancer potential through induction of cell death. We previously demonstrated that sanguinarine treatment at a low level induced apoptosis or programmed cell death (PCD) in the Bcl-2 low-expressing K562 human erythroleukemia cells, and that a high level induced blister cell death (BCD); whereas Bcl-2 overexpressing, sanguinarine-treated JM1 pre-B lymphoblastic cells displayed neither apoptosis nor BCD morphologies. Here, we report that sanguinarine-treated K562 cells, when analyzed by western blot, showed significant increase in expression of the pro-apoptotic Bax protein in apoptosis, but not in BCD. cDNA expression array of PCD in K562 cells failed to reveal the presence of Bax at the gene transcript level, which suggests that this cell death process does not require de novo protein synthesis. Treated JM1 cells, on the other hand, showed an increase in the expression of Bcl-2 protein in both forms of cell death, but failed to show Bax expression. The role of other members of the Bcl-2 family remained negligible. Caspase-3 activation was observed in apoptosis of K562 cells but not in BCD or in sanguinarine-treated JM1 cells. These results suggest that sanguinarine in K562 cells induces apoptosis through increasing Bax and activating caspase-3, whereas sanguinarine-induced BCD involves neither. These results also suggest that in JM1 cells, Bcl-2 may play a role in susceptibility of cells to induction of apoptosis and BCD.

Abstract: A case of sternal cleft is presented in which an iliac bone graft was used to repair a defect of the lower two-thirds of the sternum together with a local rotation flap for wound closure. A second operation was necessary due to loss of the flap tip. At 2-year follow-up there was some absorption of the grafted iliac bone. The pertinent literature is reviewed and therapeutic principles are discussed.

Two patients with giant cell tumour of the lateral tibial condyle underwent en bloc resection and reconstruction by pedicled vascularized fibular graft. Both had good functional results and rapid solid bony union. This procedure preserved the lateral stabilizing structures of the knee, allowed relatively early mobilization and provided some cartilagionous surface for articulation with the lateral femoral condyle. The procedure was technically simple compared with homograft reconstruction, prosthetic replacement or free vascularized bone grafts, and could be performed in less sophisticated centres. The operation also provided additional bone stock for subsequent fusion if necessary.

A design procedure for a car trunk deck-lid using an approximate optimization technique is presented. Selecting the deck-lid gages and deck-lid inner panel configuration as design variables and overall stiffnesses as constraints, a possible weight reduction of 20 percent is demonstrated, compared with the base production deck-lid design. Although other practical design constraints might not allow one to achieve this goal, the potential value of optimization techniques is clearly demonstrated by this study. It is concluded that it could be useful to develop and apply such a procedure to components such as hoods, deck-lids, doors, and fenders, which are isolatable as structural components.

An adolescent boy with essential hypernatreamia, absent corpus callosum, mental retardation, hypodipsia, and partial diabetes insipidus with 'inappropriate' ADH regulation and secretion was studied regarding factors controlling ADH and neurophysin release. Persistent hyperosmolality was noted while on 100 mEq sodium intake daily. Endogenous vasopressin activity was demonstrated after prolonged water deprivation. Hypertonic saline infusion produced increased volumes but dilute urine. Aqueous pitressin increased urinary osmolality, decreased serum osmolality, urine flow rate, and free water clearance. Stable water diuresis was induced by water loading and on normal saline infusion. Nicotine-stimulated neurophysin remained unexpectedly low and below the level of detectability when sampled during the physiologic studies, whereas oestrogen-stimulated neurophysin was elevated during oestrogen stimulation, water loading, and orthostasis procedures. Plasma vasopressin was suppressed with water loading but remained suppressed 90 min after tilt table testing. These data indicate impairment of the osmoreceptor mechanism; however, since the patient had a normal response of oestrogen-stimulated neurophysin, that part of the neurohypophysis appears intact. Chlorpropamide was effective in alleviating the hyperosmolar state acutely and maintained normal osmolar concentrations during two years of therapy.

For power-law hardening materials, a stress resultant constitutive law of incremental plasticity nature for thin plates is constructed. The yield function in the stress resultant space is approximated in quadratic form and an equivalent stress resultant is defined. One of two parameters in the yield function is analytically determined based on the concept of complementary potential surface. The other is determined by the least square method to fit the complementary potential surface of Chou et al., (1991). In analogy to the work of Hill (1979), the equivalent work-conjugate generalized plastic strain rate is derived. Finally, the hardening rule between the equivalent stress resultant and generalized plastic strain is obtained based on the results of Chou et al. (1991) for power-law materials under proportional straining conditions.

We have studied, as part of a group of international multicente phase H clinical trials, the toxicity and effectiveness of CAMPATH1H administered intravenously three times a week in an outpatient setting to patients with recurrent or progressive low grade lymphoma. We report here on the toxicity and therapeutic results of the first seven patients treated before the study was closed prematurely because of unacceptable toxicity. Classical complete or partial responses of treatment were seen in three of seven patients. One complete response lasted 8.5 months and the other complete response is ongoing at 1 year. Responses occurred in nodal sites as well as in skin and peripheral blood. The first three or four antibody infusions in each patient was associated with grade 1 or 2 side-effects including rigor, fever, facial flushing, nausea, vomiting, hives, wheezes, hypotension, andlor diarrhea but these subsequently decreased or disappeared. The most significant toxicity was profound lymphopenia and associated infection, usually viral. Six of seven patients had culture or serologically documented infections and four patients had two or more such episodes. All infections responded to temporary discontinuation of antibody therapy and appropriate antiviral or antibiotic agents. We conclude that CAMPATH1H monoclonal antibody has therapeutic activity against low grade non-Hodgkin's lymphoma but that this activity is limited by marked lymphopenia and an unacceptably high frequency of serious infection at the dose and schedule used in this trial.

Three phenomenological yield criteria are adopted to describe the plastic behaviour of sheet metals with normal plastic anisotropy. The sheet metals are assumed to be elastic-plastic, rate-sensitive and incompressible. A rate-sensitive thin shell finite element formulation based on the virtual work principle is derived for the three yield criteria. The effects of the yield surface shapes based on the three yield criteria with the same value of the plastic anisotropy parameter R on the strain distribution and localization are investigated under a hemispherical punch stretching operation and a plane strain rawing operation. The results of the simulations show that the yield surface shape, in addition to the plastic anisotropy parameter R, controls the punch force, strain distribution and strain localization for the punch stretching operation. However, the yield surface shape does not affect the punch force and the strain distribution significantly for the plane strain drawing operation. © 1998 John Wiley & Sons, Ltd.

The p16 (MTS1) tumour-suppressor gene is a cyclin-dependent kinase (cdk) inhibitor that decelerates the cell cycle by inactivating the cdks that phosphorylate the retinoblastoma tumour-suppressor gene (Rb) protein (pRb). In cervical cancers, pRb is inactivated by the HPV E7 oncoprotein or by mutations. The hypothesis of earlier reports was that the disruption of the p16/cdk-cyclin/Rb cascade is essential for malignant cervical transformation/carcinogenesis. We previously established in vitro model systems of cervical cancer representing four steps of oncogenic progression initiated by the two most common oncogenic HPVs in ectocervical and endocervical epithelial cells. This report used these systems to investigate the role of p16 in cervical cancers. A dramatic enhancement of the p16 RNA level was observed after immortalization by HPV 16 or 18. Furthermore, the p16 protein was newly observed following immortalization. However, no further changes were found for RNA or protein levels after serum selection or malignant transformation. For three cervical carcinoma cell lines, similar high levels of p16 expression were seen. Point mutations or homozygous deletions of p16 were not observed in the in vitro systems or in clinical specimens. These results suggest that the inactivation of the p16/cdk-cyclin/Rb cascade does not occur during malignant transformation but occurs during the immortalization by HPV in HPV-harbouring premalignant lesions, the in situ equivalent of immortalized cells. Also suggested is that p16 has no role in the specific malignant transformation step from immortal premalignant lesions during the carcinogenesis of HPV-initiated cervical cancers.

Monoclonal antibodies to the CD9 antigen are powerful platelet agonists. We report here the novel finding that the anti-CD9 monoclonal antibodies 50H.19 and ALB6promote physical association between CD9 antigen and the glycoprotein Hb-IIIa complex (GPIIb-IIa) component of the platelet fibrinogen receptor. The monoclonal antibodies do not consistently immunoprecipitate proteins other than CD9 from 125I-labeled human platelets even if the platelets are first treated with the homobifunctional cross-linking reagent dithiobis(succinimidyl propionate), indicating that CD9 antigen is not physically associated with other membrane proteins in the resting state. However, the addition of agonistic concentrations of either monoclonal antibody before cross-linking results in the co-precipitation of proteins corresponding in mobility and peptide composition to GPIIb, and GPIIIa. The association of CD9 with the GPIIb-IIIa complex is unaffected by a combination of aspirin and ADP scavengers sufficient to abrogate anti-CD9 monoclonal antibody-induced platelet aggregation, and is therefore not dependent upon thromboxane- and ADP-mediated pathways of intracellular signalling. The specificity of the association is demonstrated by the lack of other co-precipitating major proteins, by the requirement for induction by anti-CD9 monoclonal antibodies, and by the failure to promote reciprocal association with either of the anti-GPIIb-IIIa complex monoclonal antibodies P2 or HuP1-m1a.

In this paper the optimal cross-sectional shape of a thin-walled composite tube for maximum torsional rigidity is studied. Optimality conditions are presented, using variational principles. Due to unknown end points, transver-sality conditions are used to find boundary conditions. It is shown that a circular section is the optimal shape for a tube with helically-wound reinforced composite material. For an orthotropic tube, the optimal shape is found to be C continuous only for cases in which the degree of orthotropism is less than or equal to a critical value. Otherwise, the optimal shape contains cusps at the end points.