Interfacial cavitation.

Cavitation has long been recognized as a crucial predictor, or precursor, to the ultimate failure of various materials, ranging from ductile metals to soft and biological materials. Traditionally, cavitation in solids is defined as an unstable expansion of a void or a defect within a material. The critical applied load needed to trigger this instability -- the critical pressure -- is a lengthscale independent material property and has been predicted by numerous theoretical studies for a breadth of constitutive models. While these studies usually assume that cavitation initiates from defects in the bulk of an otherwise homogeneous medium, an alternative and potentially more ubiquitous scenario can occur if the defects are found at interfaces between two distinct media within the body. Such interfaces are becoming increasingly common in modern materials with the use of multimaterial composites and layer-by-layer additive manufacturing methods. However, a criterion to determine the threshold for interfacial failure, in analogy to the bulk cavitation limit, has yet to be reported. In this work, we fill this gap. Our theoretical model captures a lengthscale independent limit for interfacial cavitation, and is shown to agree with our observations at two distinct lengthscales, via two different experimental systems. To further understand the competition between the two cavitation modes (bulk versus interface), we expand our investigation beyond the elastic response to understand the ensuing unstable propagation of delamination at the interface. A phase diagram summarizes these results, showing regimes in which interfacial failure becomes the dominant mechanism.

Observation of Ultraslow Shock Waves in a Tunable Magnetic Lattice.

The combination of fast propagation speeds and highly localized nature has hindered the direct observation of the evolution of shock waves at the molecular scale. To address this limitation, an experimental system is designed by tuning a one-dimensional magnetic lattice to evolve benign waveforms into shock waves at observable spatial and temporal scales, thus serving as a "magnifying glass" to illuminate shock processes. An accompanying analysis confirms that the formation of strong shocks is fully captured. The exhibited lack of a steady state induced by indefinite expansion of a disordered transition zone points to the absence of local thermodynamic equilibrium and resurfaces lingering questions on the validity of continuum assumptions in the presence of strong shocks.

Connexin and gap junctions: perspectives from biology to nanotechnology based therapeutics.

The concept of gap junctions and their role in intercellular communication has been known for around 50 years. Considerable progress has been made in understanding the fundamental biology of connexins in mediating gap junction intercellular communication (GJIC) and their role in various cellular processes including pathological conditions. However, this understanding has not led to development of advanced therapeutics utilizing GJIC. Inadequacies in strategies that target specific connexin protein in the affected tissue, with minimal or no collateral damage, are the primary reason for the lack of development of efficient therapeutic models. Herein, nanotechnology has a role to play, giving plenty of scope to circumvent these problems and develop more efficient connexin based therapeutics. AsODN, antisense oligodeoxynucleotides; BMPs, bone morphogenetic proteins; BMSCs, bone marrow stem cells; BG, bioglass; Cx, Connexin; CxRE, connexin-responsive elements; CoCr NPs, cobalt-chromium nanoparticles; cGAMP, cyclic guanosine monophosphate-adenosine monophosphate; cAMP, cyclic adenosine monophosphate; ERK1/2, extracellular signal-regulated kinase 1/2; EMT, epithelial-mesenchymal transition; EPA, eicosapentaenoic acids; FGFR1, fibroblast growth factor receptor 1; FRAP, fluorescence recovery after photobleaching; 5-FU, 5-fluorouracil; GJ, gap junction; GJIC, gap junctional intercellular communication; HGPRTase, hypoxanthine phosphoribosyltransferase; HSV-TK, herpes virus thymidine kinase; HSA, human serum albumin; HA, hyaluronic acid; HDAC, histone deacetylase; IRI, ischemia reperfusion injury; IL-6, interleukin-6; IL-8, interleukin-8; IONPs, iron-oxide nanoparticles; JNK, c-Jun N-terminal kinase; LAMP, local activation of molecular fluorescent probe; MSCs, mesenchymal stem cells; MMP, matrix metalloproteinase; MI, myocardial infarction; MAPK, mitogen-activated protein kinase; NF-κB, nuclear factor kappa B; NO, nitric oxide; PKC, protein kinase C; QDs, quantum dots; ROI, region of interest; RGO, reduced graphene oxide; siRNA, small interfering RNA; TGF-ß1, transforming growth factor-ß1; TNF-α, tumor necrosis factor-α; UCN, upconversion nanoparticles; VEGF, vascular endothelial growth factor. In this review, we discuss briefly the role of connexins and gap junctions in various physiological and pathological processes, with special emphasis on cancer. We further discuss the application of nanotechnology and tissue engineering in developing treatments for various connexin based disorders.

TiO2 doped chitosan/poly (vinyl alcohol) nanocomposite film with enhanced mechanical properties for application in bone tissue regeneration.

Here, TiO2 nanoparticles have been doped into the polymer film-construct of Chitosan/poly (vinyl alcohol)/Nano-hydroxyapatite (CPHT I - III) to enhance the mechanical and biological properties of the film so as to mimic the human bone extracellular matrix for application in human bone regeneration. The synthesized films are highly porous in nature along with the presence of macrovoids. Significantly enhanced mechanical properties were obtained upon the addition of TiO2 in comparison to previous literature. Increasing content of n-HAP-TiO2 increased the elasticity, tensile strength of the films and the antibacterial efficacy against both Gram-Positive and Gram-Negative Bacteria. The pH of CPHT I-III films in saline remained in the low alkalinity range of (7.48-7.53) on day 14. CPHT I-III films were compatible with the human erythrocytes as their hemolysis was well below the limit of acute hemolysis. The in-vitro studies revealed the highly cytocompatible nature of CPHT III (15% n-HAP-TiO2) for osteoblast-like MG - 63 cell attachment and proliferation. The study has revealed that CPHT III has the potential to be used for bone tissue regeneration, our future studies will be focused on the in-vivo investigations to establish its use in clinical settings.

Connexin-43 enhances tumor suppressing activity of artesunate via gap junction-dependent as well as independent pathways in human breast cancer cells.

The gap junction (GJ) protein connexin-43 (Cx43) is considered as a tumour suppressor protein for its role in reversing the phenotype of the cancer cells. In this study, we exploited the antitumor property of Cx43 in conjunction with the artesunate (ART), a plant-based active anti-malarial compound. The reactive oxygen species (ROS) generated by ART resulted in DNA damage, which in turn led to DNA damage response by activation of DNA damage repair proteins. GJ deficient MCF-7 cells transfected with Cx43 gene showed an increased sensitivity towards dose-dependent ART treatment and required a significantly lower dose of ART to attain its IC50, as compared to parental cells. This would ultimately result in reduced dose-dependent side effects of ART. The Co-culture experiments involving GJ intercellular communication (GJIC) deficient and GJIC enabled cells, established the transfer of ROS to the neighbouring cancer cells not exposed to ART. The ROS accumulated in the ART-treated cells induced the oxidative damage in neighbouring cells, leading to bystander cell death and inhibition of bystander cell proliferation. Thus, our study revealed that expression of Cx43 helped in reducing the dose-dependent cytotoxicity of ART as well as enhanced the bystander apoptosis of the neighbouring cells.

LGR5 regulates pro-survival MEK/ERK and proliferative Wnt/ß-catenin signalling in neuroblastoma.

LGR5 is a marker of normal and cancer stem cells in various tissues where it functions as a receptor for R-spondins and increases canonical Wnt signalling amplitude. Here we report that LGR5 is also highly expressed in a subset of high grade neuroblastomas. Neuroblastoma is a clinically heterogenous paediatric cancer comprising a high proportion of poor prognosis cases (~40%) which are frequently lethal. Unlike many cancers, Wnt pathway mutations are not apparent in neuroblastoma, although previous microarray analyses have implicated deregulated Wnt signalling in high-risk neuroblastoma. We demonstrate that LGR5 facilitates high Wnt signalling in neuroblastoma cell lines treated with Wnt3a and R-spondins, with SK-N-BE(2)-C, SK-N-NAS and SH-SY5Y cell-lines all displaying strong Wnt induction. These lines represent MYCN-amplified, NRAS and ALK mutant neuroblastoma subtypes respectively. Wnt3a/R-Spondin treatment also promoted nuclear translocation of ß-catenin, increased proliferation and activation of Wnt target genes. Strikingly, short-interfering RNA mediated knockdown of LGR5 induces dramatic Wnt-independent apoptosis in all three cell-lines, accompanied by greatly diminished phosphorylation of mitogen/extracellular signal-regulated kinases (MEK1/2) and extracellular signal-regulated kinases (ERK1/2), and an increase of BimEL, an apoptosis facilitator downstream of ERK. Akt signalling is also decreased by a Rictor dependent, PDK1-independent mechanism. LGR5 expression is cell cycle regulated and LGR5 depletion triggers G1 cell-cycle arrest, increased p27 and decreased phosphorylated retinoblastoma protein. Our study therefore characterises new cancer-associated pathways regulated by LGR5, and suggest that targeting of LGR5 may be of therapeutic benefit for neuroblastomas with diverse etiologies, as well as other cancers expressing high LGR5.

Macrophage colony-stimulating factor and cancer: a review.

Tumor growth is influenced by a wide variety of external and internal factors. One of the most important mediators of tumor development is our immune system. The nonstop surveillance of the immune system was originally expected to clear the transformed cells from the body and guard against the development of tumor. But contradictory evidences are reported to show the involvement of immune system in supporting the growth and spread of tumor. Tumor infiltrating immune cells, in addition to harboring immunosuppressive activities, also promote angiogenesis and metastasis of tumor. Many growth factors and cytokines are involved in shaping this complex immune microenvironment of the tumor. Macrophage colony-stimulating factor (MCSF) is one such growth factor which is overexpressed in many tumors. In this review, we summarize the basic biology of MCSF, its role in cancer and discuss the involvement of tumor-associated macrophages (TAMs) in tumor development.

Silver nanoparticles impregnated alginate-chitosan-blended nanocarrier induces apoptosis in human glioblastoma cells.

Herein, a green method for the development of a novel biodegradable silver nanoparticles (NPs) impregnated alginate-chitosan-blended nanocarrier (Ag NPs-Alg-Chi NC) is reported. The synthesis of Ag NPs-Alg-Chi NC is based on the polyelectrolyte complex formation between alginate and chitosan. The composite NC is characterized by ultraviolet-visible spectroscopy, transmission electron microscopy, scanning electron microscopy (SEM), Fourier transform infrared spectroscopy, and X-ray diffraction. The Ag NPs in the NC are found to elicit anticell proliferative effect on refractory U87MG (human glioblastoma) cells at IC50 of 2.4 µg mL(-1) for Ag NPs. The cell cycle analysis shows extensive DNA damage. Elevation in reactive oxygen species level indicates induction of oxidative stress in treated cells. Mitochondrial dysfunction in cell death is evident from the depolarization of mitochondrial membrane potential (ΔΨm ). Fluorescence and SEM images of the treated cells reveal nuclear and morphological changes characteristic of apoptosis, which is further confirmed by TUNEL assay. The induction of apoptosis at low concentration of Ag NPs present in Ag NPs-Alg-Chi NC in comparison with free Ag NPs makes it a promising tool for cancer therapy.

Amelioration of cancer stem cells in macrophage colony stimulating factor-expressing U87MG-human glioblastoma upon 5-fluorouracil therapy.

Macrophage colony stimulating factor (MCSF) regulates growth, proliferation and differentiation of haematopoietic cell lineages. Many cancers are known to secrete high level of MCSF, which recruit macrophages into the tumour micro-environment, supporting tumour growth. Herein, we report the cloning of MCSF and subsequent generation of U87MG expressing MCSF stable cell line (U87-MCSF). Cytotoxicity of anti-cancer drug 5-fluorouracil (5-FU) was evaluated on both U87MG and U87-MCSF cells. Interestingly, the proliferation of U87-MCSF cells was less (p<0.001) than that of U87MG cells alone, after treatment with 5-FU. Significant decrease in expression levels of cyclin E and A2 quantified by real time PCR analysis corroborated the reduced proliferation of 5-FU treated U87-MCSF cells. However, JC-1 staining did not reveal any apoptosis upon 5-FU treatment. Notch-1 upregulation induced a possible epithelial-mesenchymal transition in U87-MCSF cells, which accounted for an increase in the proportion of CD24(high)/CD44(less) cancer stem cells in U87-MCSF cells after 5-FU treatment. The elevated resistance of U87-MCSF cells towards 5-FU was due to the increase in the expressions (10.2 and 6 fold) of ABCB1 and mdm2, respectively. Furthermore, increase in expressions of ABCG1, mdm2 and CD24 was also observed in U87MG cells after prolonged incubation with 5-FU. Our studies provided mechanistic insights into drug resistance of U87MG cells and also described the pivotal role played by MCSF in augmenting the resistance of U87MG cells to 5-FU.

Visualizing individual nitrogen dopants in monolayer graphene.

In monolayer graphene, substitutional doping during growth can be used to alter its electronic properties. We used scanning tunneling microscopy, Raman spectroscopy, x-ray spectroscopy, and first principles calculations to characterize individual nitrogen dopants in monolayer graphene grown on a copper substrate. Individual nitrogen atoms were incorporated as graphitic dopants, and a fraction of the extra electron on each nitrogen atom was delocalized into the graphene lattice. The electronic structure of nitrogen-doped graphene was strongly modified only within a few lattice spacings of the site of the nitrogen dopant. These findings show that chemical doping is a promising route to achieving high-quality graphene films with a large carrier concentration.

Madurai Area Physicians Cardiovascular Health Evaluation Survey (MAPCHES)--an alarming status.

BACKGROUND: Studies have shown that South Asians are highly susceptible to cardiovascular diseases (CVDs). There is very little information available about the prevalence of risk factors for CVD in the physician population, a group that might be expected to be more aware of cardiovascular risk and health status. AIM: To evaluate the prevalence of cardiovascular risk factors - including metabolic, dietary and behavioural - among the physician population in southern India. METHODS: Approximately 4000 physicians of differing specialties from eight southern districts in Tamilnadu, India, in and around the city of Madurai were listed. Of these, 1600 were randomly selected to participate in a cross-sectional survey, of which 1514 physicians agreed to participate. The survey included demographic questionnaires, objective measurements of blood pressure, fasting blood sugar, fasting lipids and waist circumference, and questionnaires about their dietary and behavioural habits. RESULTS: Complete data were available for 1433 physicians. Using a blood pressure cut-off value of 130/85 mmHg or higher, the study recorded a prevalence of 41% among men and 23% among women. On applying the International Diabetes Federation criteria for the metabolic syndrome for the South Asian population, the present study identified 49% of female physicians and 41% of male physicians as having the metabolic syndrome. Only 17% were physically active. Less than one-half of them consumed vegetables. Nearly 31% of male physicians were smokers. CONCLUSION: Analysis of these data suggests that the risk for CVD and stroke is at epidemic proportions in a cohort of well-educated physicians who are in the highest quintile of income.

A new behaviour of ac losses in superconducting Bi(2)Sr(2)CaCu(2)O(8) single crystals.

A new ac loss behaviour is observed in the superconducting state of Bi(2)Sr(2)CaCu(2)O(8) single crystals using a novel technique of measuring dissipation at radio frequencies. It is found that the ac loss in the superconducting state is larger than that in the normal state. This counter-intuitive result is explained in terms of the cumulative effect of repetitive decoupling of intrinsic Josephson junctions in the crystals and analysed in the framework of Ambegaokar-Baratoff theory. The ac losses are studied as a function of temperature, rf amplitude and magnetic field applied at different orientations. A peak in ac losses is observed in the superconducting state along the temperature scale. The amplitude of the peak decreases and shifts towards lower temperature with increasing field and also when the field orientation with respect to the c axis of the crystal changes from the perpendicular to parallel direction. The origin of the peak and its behaviour are discussed in the context of coupling energy of Josephson junctions present in the sample. In the presence of a magnetic field another peak in ac losses arises at temperatures close to T(c), which is associated with the Lorentz-force-driven motion of vortices.

Competing effects of surface phonon softening and quantum size effects on the superconducting properties of nanostructured Pb.

The superconducting transition temperature (T(C)) in nanostructured Pb decreases from 7.24 to 6.4 K as the particle size is reduced from 65 to 7 nm, below which superconductivity is lost rather abruptly. In contrast, there is a large enhancement in the upper critical field (H(C2)) in the same size regime. We explore the origin of the unusual robustness of T(C) over such a large particle size range in nanostructured Pb by measuring the temperature dependence of the superconducting energy gap in planar tunnel junctions of Al/Al(2)O(3)/nano-Pb. We show that below 22 nm, the electron-phonon coupling strength increases monotonically with decreasing particle size, and almost exactly compensates for the quantum size effect, which is expected to suppress T(C).

The effect of stimulant laxatives and polyethylene glycol-electrolyte lavage solution for colonoscopy preparation on serum electrolytes and hemodynamics.

We have previously shown that magnesium citrate or bisacodyl before polyethylene glycol electrolyte lavage solution (PEG-ELS) improves colonoscopy preparation. Patients prefer this to preparation with full-volume PEG-ELS alone. However, such combinations might cause undesirable changes in hemodynamics or serum electrolytes. This study examined the effects of these combinations on heart rate, blood pressure, and serum electrolytes. We randomized 68 consecutive patients undergoing colonoscopy to one of three preparations. Group 1 received 4 L of PEG-ELS, group 2 received 2 L of PEG-ELS with 20 mg bisacodyl, and group 3 received 2 L of PEG-ELS preceded by 296 mL of magnesium citrate. Heart rate, blood pressure, and serum electrolytes were measured before starting the preparation and immediately before colonoscopy. Mean serum magnesium fell by 0.01 mg/dL and 0.11 mg/dL in groups 1 and 2, respectively, and rose by 0.06 mg/dL in group 3 (p = 0.044). There were no other significant changes. Statistically significant changes in serum magnesium after preparation with PEG-ELS and a stimulant laxative are minor and probably of no clinical relevance. Two liters of PEG-ELS with a stimulant laxative is safe and effective for colonoscopy.

The outcome of cemented vs. cementless fixation of a femoral component in total knee replacement (TKR) with the identification of radiological signs for the prediction of failure.

A survival analysis and radiological review were performed on a series of femoral total knee arthroplasty (TKA) prostheses either cemented (150 cases) or cementless, press-fit (201 cases). The internal surface of the femoral components were shot-blast CoCr alloy. The incidence of loosening of the femoral component at 6 years was 9.8% with cementless fixation and 0.6% with cement (P<0.05) at 6 years. Amongst uncemented prostheses, there was no difference in the survival or radiological outcome with the use of a stem as against two condylar pegs. The clinical need for revision may be predicted radiologically 3 years after operation in symptomless patients by noting a change in component position combined with progressive radiolucent lines and osteolysis. Thus, radiological follow-up should be continued for a minimum of 3 years after knee replacement. The use of a stem enabled the detection of radiolucent lines which we believe were missed around prostheses with condylar pegs. Thus, the use of a stem improves the prediction of failure (but does not improve fixation).

Toxic and sublethal effects of endosulfan and carbaryl on growth and egg production of Moina micrura Kurz (Cladocera: Moinidae).

The toxic and sublethal effects of endosulfan and carbaryl on a cladoceran, Moina micrura, were studied. The dosage-mortality regression lines gave LC(50) values for the pesticides. The cumulative growth and egg production during life were inhibited to 31.8 and 20.7% in endosulfan, and 28.2 and 13.7% in carbaryl-treated animals, respectively. The growth coefficient (K value) and the intrinsic rate of natural increase per day (r value) of control M. micrura were 0.144 and 0.377, respectively; these decreased to 0.121 and 0.346 in carbaryl-, and 0.073 and 0.356 in endosulfan-treated animals, respectively.