Role of microstructure in the grinding and polishing of α-sialon ceramics

The grinding and polishing behaviour of three tailored α-sialon microstructures made of the same chemical composition: fine-grained, bimodal and large elongated-grained, were determined. The fine-grained microstructure was characterised by extensive lateral cracks in the grinding process and widespread grain pullout during the mechanical polishing; in contrast, the large elongated-grained microstructure exhibited high grinding damage resistance, and a defect-free, mirror-like surface after mechanical polishing. The bimodal microstructure showed an intermediate behaviour during both processes. The material removal mechanisms during grinding and polishing were analysed and modelled as a function of grain size and aspect ratio.     

The Other Side of the Coin: May Androgens Have a Role in Breast Cancer Risk?

Breast cancer prevention is a major challenge worldwide. During the last few years, efforts have been made to identify molecular breast tissue factors that could be linked to an increased risk of developing the disease in healthy women. In this concern, steroid hormones and their receptors are key players since they are deeply involved in the growth, development and lifetime changes of the mammary gland and play a crucial role in breast cancer development and progression. In particular, androgens, by binding their own receptor, seem to exert a dichotomous effect, as they reduce cell proliferation in estrogen receptor α positive (ERα+) breast cancers while promoting tumour growth in the ERα negative ones. Despite this intricate role in cancer, very little is known about the impact of androgen receptor (AR)-mediated signalling on normal breast tissue and its correlation to breast cancer risk factors. Through an accurate collection of experimental and epidemiological studies, this review aims to elucidate whether androgens might influence the susceptibility for breast cancer. Moreover, the possibility to exploit the AR as a useful marker to predict the disease will be also evaluated.     

The Design of Potent,Selective and Drug-Like RGD αvβ1 Small-Molecule Inhibitors Derived from non-RGD α4β1 Antagonists

Up to 45 % of deaths in developed nations can be attributed to chronic fibroproliferative diseases, highlighting the need for effective therapies. The RGD (Arg-Gly-Asp) integrin αvβ1 was recently investigated for its role in fibrotic disease, and thus warrants therapeutic targeting. Herein we describe the identification of non-RGD hit small-molecule αvβ1 inhibitors. We show that αvβ1 activity is embedded in a range of published α4β1 (VLA-4) ligands; we also demonstrate how a non-RGD integrin inhibitor (of α4β1 in this case) was converted into a potent non-zwitterionic RGD integrin inhibitor (of αvβ1 in this case). We designed urea ligands with excellent selectivity over α4β1 and the other αv integrins (αvβ3, αvβ5, αvβ6, αvβ8). In silico docking models and density functional theory (DFT) calculations aided the discovery of the lead urea series.     

Involvement of Ca2+ Signaling in the Synergistic Effects between Muscarinic Receptor Antagonists and β2-Adrenoceptor Agonists in Airway Smooth Muscle

Long-acting muscarinic antagonists (LAMAs) and short-acting β₂-adrenoceptor agonists (SABAs) play important roles in remedy for COPD. To propel a translational research for development of bronchodilator therapy, synergistic effects between SABAs with LAMAs were examined focused on Ca²⁺ signaling using simultaneous records of isometric tension and F340/F380 in fura-2-loaded tracheal smooth muscle. Glycopyrronium (3 nM), a LAMA, modestly reduced methacholine (1 μM)-induced contraction. When procaterol, salbutamol and SABAs were applied in the presence of glycopyrronium, relaxant effects of these SABAs are markedly enhanced, and percent inhibition of tension was much greater than the sum of those for each agent and those expected from the BI theory. In contrast, percent inhibition of F340/F380 was not greater than those values. Bisindolylmaleimide, an inhibitor of protein kinase C (PKC), significantly increased the relaxant effect of LAMA without reducing F340/F380. Iberiotoxin, an inhibitor of large-conductance Ca²⁺-activated K⁺ (K_Ca) channels, significantly suppressed the effects of these combined agents with reducing F340/F380. In conclusion, combination of SABAs with LAMAs synergistically enhances inhibition of muscarinic contraction via decreasing both Ca²⁺ sensitization mediated by PKC and Ca²⁺ dynamics mediated by K_Ca channels. PKC and K_Ca channels may be molecular targets for cross talk between β₂-adrenoceptors and muscarinic receptors.     

The Use of Ultrasonics in the Treatment of Waste Activated Sludge

1 INTRODUCTION Waste activated sludge (WAS) processes are key technologies to treat wastewater. Through their micro-bial activity, these biological processes produce how-ever huge amounts of WAS as an inevitable drawback of the WAS-process. Various techniques have been studied to further reduce the amount of excess sludge through (1) the maximum use of biological phospho-rus removal instead of chemical precipitation[1,2]; (2) the use of advanced treatment techniques such as per-oxidati…     

The Role of the Liquid‐Solid Interface in the Preparation of Supported Catalysts

The contribution of the Interface Science to the preparation of supported catalysts during the last two decades is presented. It is illustrated how the concepts and the methodologies of the Interface Science could be effectively used for an in‐depth understanding of the phenomena involved in the initial preparation step. This, extremely critical step, concerns the deposition of transition metal species containing the active elements, from an impregnation solution, onto the surface of common catalytic supports. Moreover, the aforementioned concepts and methodologies allow the regulation of the mode of interfacial deposition and the local structure of the deposited species and, thus, the surface characteristics and the catalytic behaviour of the resulted catalysts.     

The Treatment of Dyslipidemia—What's Left in the Pipeline?

Dyslipidemia is a pathological alteration of serum lipid levels. The most common forms are either elevations of triglycerides or low density lipoprotein cholesterol associated with a reduction of high density lipoprotein cholesterol. Most frequently both forms of lipid disorders are combined. Elevations of free fatty acid blood levels are commonly not subsumed under the term dyslipidemia. However, free fatty acids should also be considered, as they are frequently associated with dyslipidemia and represent a risk factor for cardiovascular diseases. Dyslipidemias are among the major etiologic factors for arterial occlusive diseases. Resulting in fatal implications such as stroke and coronary heart disease, dyslipidemias contribute to the most prevalent causes of death. Lowering of low density lipoprotein and raising of high density lipoprotein cholesterol levels have been shown in both epidemiologic and intervention studies to decrease mortality. Established treatments of dyslipidemias are statins and fibrates. However, recent research has established some new potential therapeutic targets which are currently investigated in clinical trials. New therapeutic approaches include subtype selective, dual, and pan-agonists of the peroxisome proliferator activated receptor, inhibitors of the cholesterol ester transfer protein, Acyl-CoA-cholesterol-acyltransferase, squalene synthase, microsomal triglycerid-transfer-protein, and cholesterol absorption. Clinical implications of new drugs under investigation are discussed in this review.     

The Role of Neurotrophins in Multiple Sclerosis��Pathological and Clinical Implications

Multiple sclerosis (MS) is a chronic inflammatory demyelinating and neurodegenerative disease of the central nervous system (CNS) with unknown etiology. It was recently suggested that autoimmunity, which had long been considered to be destructive in MS, might also play a protective role in the CNS of MS patients. Neurotrophins are polypeptides belonging to the neurotrophic factor family. While neurotrophins mediate cell survival and proliferation in the nervous system, they are also expressed within peripheral blood mononuclear cells fraction (PBMCs) of immunological system. In MS additional neurotrophic support from PBMCs might compensate relative neurotrophins deficiency in the damaged CNS tissue that needs to be repaired. Failure to produce the adequate neurotrophins concentrations might result in decreased protection of the CNS, consequently leading to increased atrophy, which is the main determinant of MS patients’ end-point disability. There are several lines of evidence, both from clinical research and animal models, suggesting that neurotrophins play a pivotal role in neuroprotective and neuroregenerative processes that are often defective in the course of MS. It seems that neuroprotective strategies might be used as potentially valuable add-on therapies, alongside traditional immunomodulatory treatment in multiple sclerosis.     

Protective Role of α2HS-Glycoprotein in HBV-Associated Liver Failure

In this study, levels of plasma α2-Heremans-Schmid glycoprotein, serum tumor necrosis factor-α, serum liver function parameters and short-term mortality were measured in 100 hepatitis B patients. Release of interleukin-6 and tumor necrosis factor-α from the lipopolysaccharide-stimulated peripheral blood mononuclear cells in the presence/absence of spermine and α2-Heremans-Schmid glycoprotein were analyzed by enzyme-linked immunosorbent assay to determine the significance and potential mechanism of α2-Heremans-Schmid glycoprotein in hepatitis B virus-associated liver damage. Results showed that serum α2-Heremans-Schmid glycoprotein levels in acute-on-chronic liver failure patients were significantly lower than that in chronic hepatitis B patients or healthy controls (p < 0.05). A negative dependence between serum human α2-Heremans-Schmid glycoprotein and tumor necrosis factor-α levels was observed. Interleukin-6 and tumor necrosis factor-α levels in the lipopolysaccharide-induced peripheral blood mononuclear cell supernates were significantly reduced by spermine and/or α2-Heremans-Schmid glycoprotein. The latter two proteins jointly inhibited cytokine release. These observations suggest that plasma α2-Heremans-Schmid glycoprotein is an independent marker of liver damage and a prognostic indicator of hepatitis B virus chronicity. It may reduce liver inflammation by partially inhibiting release of inflammatory factors from activated peripheral blood mononuclear cells.     

The Role of Testosterone in the Elderly: What Do We Know?

Testosterone is the most important hormone in male health. Aging is characterized by testosterone deficiency due to decreasing testosterone levels associated with low testicular production, genetic factors, adiposity, and illness. Low testosterone levels in men are associated with sexual dysfunction (low sexual desire, erectile dysfunction), reduced skeletal muscle mass and strength, decreased bone mineral density, increased cardiovascular risk and alterations of the glycometabolic profile. Testosterone replacement therapy (TRT) shows several therapeutic effects while maintaining a good safety profile in hypogonadal men. TRT restores normal levels of serum testosterone in men, increasing libido and energy level and producing beneficial effects on bone density, strength and muscle as well as yielding cardioprotective effects. Nevertheless, TRT could be contraindicated in men with untreated prostate cancer, although poor findings are reported in the literature. In addition, different potential side effects, such as polycythemia, cardiac events and obstructive sleep apnea, should be monitored. The aim of our review is to provide an updated background regarding the pros and cons of TRT, evaluating its role and its clinical applicability in different domains.     

The Pro-Apoptotic Role of the Regulatory Feedback Loop between miR-124 and PKM1/HNF4α in Colorectal Cancer Cells

Accumulating evidence indicates that miRNA regulatory circuits play important roles in tumorigenesis. We previously reported that miR-124 is correlated with prognosis of colorectal cancer due to PKM-dependent regulation of glycolysis. However, the mechanism by which miR-124 regulates apoptosis in colorectal cancer remains largely elusive. Here, we show that miR-124 induced significant apoptosis in a panel of colorectal cancer cell lines. The mitochondrial apoptosis pathway was activated by miR-124. Furthermore, the pro-apoptotic role of miR-124 was dependent on the status of PKM1/2 level. PKM1 was required for miR-124-induced apoptosis. Via direct protein-protein interaction, PKM1 promoted HNF4α binding to the promoter region of miR-124 and transcribing miR-124. Moreover, HNF4α or PKM1 had a more dramatic effect on colorectal cancer cell apoptosis in the presence of miR-124. However, inhibition of miR-124 blocked cell apoptosis induced by HNF4α or PKM1. These data indicate that miR-124 not only alters the expression of genes involved in glucose metabolism but also stimulates cancer cell apoptosis. In addition, the positive feedback loop between miR-124 and PKM1/HNF4α plays an important role in colorectal cancer cell apoptosis; it suggests that disrupting this regulatory circuit might be a potential therapeutic tool for colorectal cancer treatment.     

The Effects of Ants on the Entomophagous Butterfly Caterpillar Feniseca tarquinius, and the Putative Role of Chemical Camouflage in the Feniseca–Ant Interaction

Butterfly caterpillars in the lycaenid subfamily Miletinae are predators of ant-tended Homoptera, yet they lack specialized secretory and call-production organs crucial to ant association in other lycaenids. Here, we address the question of how miletine caterpillars have invaded the ant–Homoptera symbiosis through a study of the only New World miletine, Feniseca tarquinius, a predator of the wooly aphid Prociphilus tesselatus. Previous interpretations have suggested that F. tarquinius and other miletine caterpillars avoid ant aggression by concealing themselves under silken webs. In contrast, our field data indicate that F. tarquinius caterpillars are less likely to be concealed in the presence of the ants Camponotus pennsylvanicus and Formica obscuriventris than in the absence of ants, although caterpillar and ant behaviors vary between years. Chemical analysis and behavioral assays suggest that chemical camouflage, not physical concealment, is responsible for the ants’ failure to detect and remove F. tarquinius caterpillars from aphid colonies. Analyses by gas chromatography indicate that the cuticular lipid composition of caterpillars are similar to that of their aphid prey, although it varies with prey species. Behavioral assays confirm that solvent extracts of F. tarquinius caterpillars and P. tesselatus aphids evoke similar behavioral responses in C. pennsylvanicus ants. Chemical camouflage is well known in social parasites of ants, but the present study represents one of a few documented cases where chemical deceit is important to interactions with ants outside the nest.     

The activation mechanism of oxalic acid on γ-alumina and the formation of α-alumina

Converting the γ phase into the α phase completely is necessary in the presintering stage of industrial alumina (Al₂O₃), which requires high temperature and energy consumption. To reduce the presintering temperature, γ-Al₂O₃ was activated by oxalic acid. XRD, ²⁷Al-MAS-NMR and TG-DSC were used to characterize the γ - alumina before and after activation, and the phase transformation was studied. The formation temperature of α-Al₂O₃ decreased to 1029 °C for oxalic acid activated γ-Al₂O₃, and the α-fraction was 100% for activated γ-Al₂O₃ at 1300 °C. After oxalic acid activation, the diffraction peak intensity of γ-Al₂O₃ decreased significantly; the results of ²⁷Al-MAS-NMR suggested that octahedral [AlO₆] in γ-Al₂O₃ was easier than tetrahedral [AlO₄] to be attacked by oxalic acid, and the formation of pentavalent [AlO₅] with higher reaction activity, which was in favour of the lowering formation temperature of α-Al₂O₃. The dissolution concentration of Al increased after oxalic acid activation, and the dissolution process was controlled by surface reactions. Oxalic acid mainly attacked the octahedral aluminium in γ-Al₂O₃ and extracted Al as three complexes of [Al(C₂O₄)]⁺, [Al(C₂O₄)₂]^- and [Al(C₂O₄)₃]^3-. Oxalic acid activated γ - Al₂O₃ with a lower phase transformation temperature has broad application prospects in the alumina industry.     

Role of α-Helical Structure in Organic Solvent-Activated Homodimer of Elastase Strain K

Recombinant elastase strain K overexpressed from E. coli KRX/pCon2(3) was purified to homogeneity by a combination of hydrophobic interaction chromatography and ion exchange chromatography, with a final yield of 48% and a 25-fold increase in specific activity. The purified protein had exhibited a first ever reported homodimer size of 65 kDa by SDS-PAGE and MALDI-TOF, a size which is totally distinct from that of typically reported 33 kDa monomer from P. aeruginosa. The organic solvent stability experiment had demonstrated a stability pattern which completely opposed the rules laid out in previous reports in which activity stability and enhancement were observed in hydrophilic organic solvents such as DMSO, methanol, ethanol and 1-propanol. The high stability and enhancement of the enzyme in hydrophilic solvents were explained from the view of alteration in secondary structures. Elastinolytic activation and stability were observed in 25 and 50% of methanol, respectively, despite slight reduction in α-helical structure caused upon the addition of the solvent. Further characterization experiments had postulated great stability and enhancement of elastase strain K in broad range of temperatures, pHs, metal ions, surfactants, denaturing agents and substrate specificity, indicating its potential application in detergent formulation.     

The Practical Application of Fractal Dimension in Water Treatment Practice–the Impact of Polymer Dosing

Abstract

The application of floc fractal dimension has been investigated in this work to determine if this parameter can have operational significance in water treatment. Natural organic matter suspensions were coagulated with aluminium sulphate and varying concentrations of a non‐ionic polymer. The fractal dimensions of the flocs formed were measured using light scattering and settling combined with image analysis. By using the correct methodology, optimum floc properties could be determined using the floc fractal dimension combined with the floc size and strength data.     

New Insights in the Pathogenesis of Multiple Sclerosis—Role of Acrolein in Neuronal and Myelin Damage

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) characterized by an inappropriate inflammatory reaction resulting in widespread myelin injury along white matter tracts. Neurological impairment as a result of the disease can be attributed to immune-mediated injury to myelin, axons and mitochondria, but the molecular mechanisms underlying the neuropathy remain incompletely understood. Incomplete mechanistic knowledge hinders the development of therapies capable of alleviating symptoms and slowing disease progression in the long-term. Recently, oxidative stress has been implicated as a key component of neural tissue damage prompting investigation of reactive oxygen species (ROS) scavengers as a potential therapeutic option. Despite the establishment of oxidative stress as a crucial process in MS development and progression, ROS scavengers have had limited success in animal studies which has prompted pursuit of an alternative target capable of curtailing oxidative stress. Acrolein, a toxic β-unsaturated aldehyde capable of initiating and perpetuating oxidative stress, has been suggested as a viable point of intervention to guide the development of new treatments. Sequestering acrolein using an FDA-approved compound, hydralazine, offers neuroprotection resulting in dampened symptom severity and slowed disease progression in experimental autoimmune encephalomyelitis (EAE) mice. These results provide promise for therapeutic development, indicating the possible utility of neutralizing acrolein to preserve and improve neurological function in MS patients.     

Collaborations between Israel and Germany in Chemistry and the Other Sciences – a Sign of Normalization?

The scientific collaboration between Israel and Germany was not initiated, as commonly believed, by the Max Planck Society or by German scientists who wanted to revive collaboration with their former Jewish colleagues. Rather, it was initiated in the mid-1950s by two Israeli scientists from the Weizmann Institute and a German scientist at the time at CERN in violation of the widely accepted cultural boycott by Israel against Germany. The initiators succeeded in procuring political support; large-scale collaboration between the Weizmann Institute, German universities, and the Max Planck Society was developed. In the aftermath of the Second World War, German science suffered from the Nazi expulsion of Jewish scientists and partial international isolation; the collaboration with Israel enabled young German scientists to overcome this isolation and benefit from stimulating Israeli research environments. In times of economic hardship, the collaboration helped Israeli science materially, provided contacts to chemical industry, and strengthened the cooperation between Israeli and European science. The collaboration was built, in part, on postwar myths created by German scientists and the Max Planck Society about their former anti-Nazi attitudes. Despite the difficult beginnings and some hidden political agendas, the collaboration developed very successfully. Germany became Israel’s second most important partner in the scientific field, after the USA. Today, normalcy prevails in many – though not all – of the Israeli-German collaborative projects; the past is not forgotten, but science is in the fore.     

Synthesis of Benzophenones and in vitro Evaluation of Their Anticancer Potential in Breast and Prostate Cancer Cells

Breast and prostate cancers are frequently treated with chemotherapy. Several novel chemicals are being reported for this purpose, particularly synthetic and natural benzophenones. This work reports the synthesis of substituted 2-hydroxybenzophenones through 1,4-conjugate addition/intramolecular cycloaddition/dehydration of nitromethane on key intermediate chromones. Structures were extensively studied by means of 2D NMR spectroscopy and single-crystal XRD. Their cytotoxicity was evaluated in vitro in two breast cancer cell lines (MDA-MB-231 and T47-D) and one prostate cancer cell line (PC3). The most potent compound exhibited good cytotoxic effects against the three cancer cell lines (IC₅₀ values ranging from 12.09 to 26.49 μm ) and induced cell-cycle retardation only on prostate cancer cells, which suggested that it might exert cell-type-specific effects.