Is alkali-carbonate reaction just a variant of alkali-silica reaction ACR = ASR?

The mechanism of the alkali-carbonate reaction (ACR) has been recognized as being different from that of the more common alkali-silica reaction (ASR). However, the identification of alkali-silica gel in ACR concrete from Cornwall, Ontario, Canada by Katayama, in 1992 raised the possibility that ASR was at least playing a role in the ACR reaction. The acid insoluble residues of the ACR aggregate from Kingston, along with two other aggregates were analyzed to determine what might be contributing to the reaction. The acid insoluble residue of the ACR Kingston rock contains 96% quartz of high solubility in NaOH. Good correlation was found between the amount of quartz and expansion of concrete prisms indicating that the expansion was due mainly to an alkali-silica reaction. This conclusion is supported by observations, in 2008, by Katayama of gel in thin sections of concrete made with the Kingston aggregate. It is concluded that ACR = ASR.     

Why Hydroxamates May Not Be the Best Histone Deacetylase Inhibitors—What Some May Have Forgotten or Would Rather Forget?

Hydroxamate‐based histone deacetylase inhibitors (HDACIs) have been approved as therapeutic agents by the US Food and Drug Administration for use in oncology applications. While the potential utility of such HDACIs in other areas of medicinal chemistry is tremendous, there are significant concerns that “pan‐HDAC inhibitors” may be too broadly acting and/or toxic for clinical use beyond oncology. In addition to the isozyme selectivity challenge, the potential mutagenicity of hydroxamate‐containing HDAC inhibitors represents a major hindrance in their application to other therapeutic areas. Herein we report on the mutagenicity of known hydroxamates, discuss the mechanisms responsible for their genotoxicity, and review some of the current alternatives to hydroxamates. We conclude that the hydroxamate group, while providing high‐potency HDACIs, is not necessarily the best zinc‐binding group for HDACI drug discovery.     

Features of Retinal Neurogenesis as a Key Factor of Age-Related Neurodegeneration: Myth or Reality?

Age-related macular degeneration (AMD) is a complex multifactorial neurodegenerative disease that constitutes the most common cause of irreversible blindness in the elderly in the developed countries. Incomplete knowledge about its pathogenesis prevents the search for effective methods of prevention and treatment of AMD, primarily of its “dry” type which is by far the most common (90% of all AMD cases). In the recent years, AMD has become “younger”: late stages of the disease are now detected in relatively young people. It is known that AMD pathogenesis—according to the age-related structural and functional changes in the retina—is linked with inflammation, hypoxia, oxidative stress, mitochondrial dysfunction, and an impairment of neurotrophic support, but the mechanisms that trigger the conversion of normal age-related changes to the pathological process as well as the reason for early AMD development remain unclear. In the adult mammalian retina, de novo neurogenesis is very limited. Therefore, the structural and functional features that arise during its maturation and formation can exert long-term effects on further ontogenesis of this tissue. The aim of this review was to discuss possible contributions of the changes/disturbances in retinal neurogenesis to the early development of AMD.     

30 Hz,Could It Be Part of a Window Frequency for Cellular Response?

Many exogenous and endogenous risk factors have been proposed as precursors of brain tumors, including the exposure to non-ionizing electromagnetic fields. Nevertheless, there is still a debate among the scientific community about the hazard of the effects produced by non-ionizing radiation (NIR) because conflicting results have been found (number of articles reviewed >50). For that reason, to provide new evidence on the possible effects produced by exposure to NIR, we performed different studies with several combinations of extremely low frequencies, times, and field intensities in tumoral and non-tumoral cells. The results of our studies showed that cell viability was frequency dependent in glioblastoma cells. In fact, our results revealed that a frequency of 30 Hz—or even other frequencies close to 30 Hz—could constitute a window frequency determinant of the cellular response in tumoral and non-tumoral cells.     

Could We Really Be Made of Swiss Cheese? Xenobiology as an Engineering Epistemology for Biological Realization

Besides having potential medical and biosafety applications, as well as challenging the foundations of biological engineering, xenobiology can also shed light on the epistemological and metaphysical questions that puzzle philosophers of science. This paper reviews this philosophical aspect of xenobiology, focusing on the possible multiple realizability of life. According to this hypothesis, what ultimately matters in understanding life is its function, not its particular building blocks. This is because there should, in theory, be many different ways to build the same function. The possibility of multiple realizability was originally raised in the context of AI's hypothesized capacity to realize mental functions. Because we still do not have any incontrovertible examples of digital minds, not to mention alien life of foreign biochemistry, the best way to test this philosophical idea is to examine the recent results and practices of synthetic biology and xenobiology.     

Management of Diabetes Mellitus: Could Simultaneous Targeting of Hyperglycemia and Oxidative Stress Be a Better Panacea?

The primary aim of the current management of diabetes mellitus is to achieve and/or maintain a glycated hemoglobin level of ≤6.5%. However, recent evidence indicates that intensive treatment of hyperglycemia is characterized by increased weight gain, severe hypoglycemia and higher mortality. Besides, evidence suggests that it is difficult to achieve and/or maintain optimal glycemic control in many diabetic patients; and that the benefits of intensively-treated hyperglycemia are restricted to microvascular complications only. In view of these adverse effects and limitations of intensive treatment of hyperglycemia in preventing diabetic complications, which is linked to oxidative stress, this commentary proposes a hypothesis that "simultaneous targeting of hyperglycemia and oxidative stress" could be more effective than "intensive treatment of hyperglycemia" in the management of diabetes mellitus.     

Etiology of IBD—Is It Still a Mystery?

Inflammatory bowel diseases (IBD), including colitis ulcerosa and Crohn’s disease, are chronic diseases of the gastrointestinal tract for which the cause has not been fully understood. However, it is known that the etiology is multifactorial. The multidirectional network of interactions of environmental, microbiological and genetic factors in predisposed persons lead to an excessive and insufficiently inhibited reaction of the immune system, leading to the development of chronic inflammation of the gastrointestinal walls, the consequence of which is the loss of the function that the intestine performs, inter alia, through the process of fibrosis. Detailed knowledge of the pathways leading to chronic inflammation makes it possible to pharmacologically modulate disorders and effectively treatthese diseases. In this review, we described the primary and adaptive immune system response in the gut and the known immune pathogenetic pathways leading to the development of IBD. We also described the process leading to intestinal tissue fibrosis, which is an irreversible consequence of untreated IBD.     

Viral Metagenomics on Animals as a Tool for the Detection of Zoonoses Prior to Human Infection?

Many human viral infections have a zoonotic, i.e., wild or domestic animal, origin. Several zoonotic viruses are transmitted to humans directly via contact with an animal or indirectly via exposure to the urine or feces of infected animals or the bite of a bloodsucking arthropod. If a virus is able to adapt and replicate in its new human host, human-to-human transmissions may occur, possibly resulting in an epidemic, such as the A/H1N1 flu pandemic in 2009. Thus, predicting emerging zoonotic infections is an important challenge for public health officials in the coming decades. The recent development of viral metagenomics, i.e., the characterization of the complete viral diversity isolated from an organism or an environment using high-throughput sequencing technologies, is promising for the surveillance of such diseases and can be accomplished by analyzing the viromes of selected animals and arthropods that are closely in contact with humans. In this review, we summarize our current knowledge of viral diversity within such animals (in particular blood-feeding arthropods, wildlife and domestic animals) using metagenomics and present its possible future application for the surveillance of zoonotic and arboviral diseases.     

Could Targeted Pharmacotherapies Exert a “Disease Modification Effect” in Patients with Chronic Plaque Psoriasis?

Chronic plaque psoriasis is an immune-mediated skin disease with a chronic relapsing course, affecting up to ~2–3% of the general adult population worldwide. The interleukin (IL)-23/Th17 axis plays a key role in the pathogenesis of this skin disease and may represent a critical target for new targeted pharmacotherapies. Cutaneous lesions tend to recur in the same body areas, likely because of the reactivation of tissue-resident memory T cells. The spillover of different pro-inflammatory cytokines into systemic circulation can promote the onset of different comorbidities, including psoriatic arthritis. New targeted pharmacotherapies may lead to almost complete skin clearance and significant improvements in the patient’s quality of life. Accumulating evidence supports the notion that early intervention with targeted pharmacotherapies could beneficially affect the clinical course of psoriatic disease at three different levels: (1) influencing the immune cells infiltrating the skin and gene expression, (2) the prevention of psoriasis-related comorbidities, especially psoriatic arthritis, and (3) the improvement of the patient’s quality of life and reduction of cumulative life course impairment. The main aim of this narrative review is to summarize the effects that new targeted pharmacotherapies for psoriasis may have on the immune scar, both at the molecular and cellular level, on psoriatic arthritis and on the patient’s quality of life.     

ATPase Inhibitory Factor 1—A Novel Marker of Cellular Fitness and Exercise Capacity?

ATPase inhibitory factor 1 is a myokine inhibiting the hydrolytic activity of mitochondrial adenosine triphosphate synthase and ecto-F1-ATPase on the surface of many cells. IF1 affects ATP metabolism in mitochondria and the extracellular space and upregulates glucose uptake in myocytes; these processes are essential in physical activity. It is unknown whether the IF1 serum concentration is associated with exercise capacity. This study explored the association between resting IF1 serum concentration and exercise capacity indices in healthy people. IF1 serum concentration was measured in samples collected at rest in 97 healthy amateur cyclists. Exercise capacity was assessed on a bike ergometer at the successive stages of the progressive cardiopulmonary exercise test (CPET). IF1 serum concentration was negatively and significantly correlated with oxygen consumption, oxygen pulse, and load at various CPET stages. A better exercise capacity was associated with lower circulating IF1. IF1 may reflect better cellular/mitochondrial energetic fitness, but there is uncertainty regarding how IF1 is released into the intravascular space. We speculate that lower IF1 concentration may reflect a better cellular/mitochondrial integrity, as this protein is bound more strongly with ATPases in mitochondria and cellular surfaces in people with higher exercise capacity.     

Late Stage C?H Activation of a Privileged Scaffold; Synthesis of a Library of Benzodiazepines

A library of over twenty 5‐(2‐arylphenyl)‐1,3‐dihydro‐2H‐1,4‐benzodiazepin‐2‐ones has been formed by a microwave‐mediated late‐stage palladium‐catalysed arylation of 1,4‐benzodiazepines using diaryliodonium salts. This can also be applied to nordazepam (7‐chloro‐5‐phenyl‐1,3‐dihydro‐2H‐1,4‐benzodiazepin‐2‐one), the active metabolite of diazepam, and subsequent N‐alkylation and/or H/D exchange allows further diversification towards elaborated pharmaceuticals and their 3,3′‐deuterated analogues.

     

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.     

Serum-Free Cultures: Could They Be a Future Direction to Improve Neuronal Differentiation of Mesenchymal Stromal Cells?

Mesenchymal stem/stromal cells (MSCs) are undifferentiated cells with multilinear potential, known for their immunomodulatory and regenerative properties. Although the scientific community is working to improve their application, concerns limit their use to repair tissues following neurological damage. One of these obstacles is represented by the use of culture media supplemented with fetal bovine serum (FBS), which, due to its xenogenic nature and the risk of contamination, has increased scientific, ethical and safety problems. Therefore, the use of serum-free media could improve MSC culture methods, avoiding infectious and immunogenic transmission problems as well as MSC bioprocesses, without the use of animal components. The purpose of our review is to provide an overview of experimental studies that demonstrate that serum-free cultures, along with the supplementation of growth factors or chemicals, can lead to a more defined and controlled environment, enhancing the proliferation and neuronal differentiation of MSCs.     

C?N Coupling of Indoles and Carbazoles with Aromatic Chlorides Catalyzed by a Single‐Component NHC‐Nickel(0) Precursor

A new and efficient nickel‐based protocol for the N‐arylation of indoles and carbazoles with aromatic chlorides, the least expensive of the aryl halides, is described. The procedure provides selectively N‐(hetero)arylation products in good to high yields, in short reaction times and without adding an excess of ligands.

     

Numerical analysis of combustion of a hydrogen–air mixture in an advanced ramjet combustor model during activation of O<Subscript>2</Subscript> molecules by resonant laser radiation

This paper presents a numerical study of the combustion of a hydrogen–air mixture in a model ramjet combustor with separate hydrogen and air supply during activation of O₂ molecules by resonant laser radiation at a wavelength of 762.3 nm and 193.3 nm. The calculation is made using the parabolized Navier–Stokes equations taking into account chemical reactions, laser irradiation, and the nonuniformity of air parameters at the combustor inlet due to the complex gas-dynamic structure of the flow in the air intake. It is shown that the combustion completeness at the combustor outlet can be increased by a factor of 2.8 by redistributing the hydrogen supply through the system of fuel tank pylons. Further increase in the combustion completeness can be obtained by exposure of a narrow flow region to resonant laser radiation, more effectively at a wavelength of 193.3 nm. The combination of laser exposure with hydrogen supply redistribution increases the combustion efficiency by a factor of more than 4.7 compared to the base case. In this case, this provides a 95% increase the longitudinal force component in the portion of the internal engine duct that provides a positive contribution to the thrust. Estimation of the energy efficiency of using laser radiation shows that the laser energy input required to achieve this effect is 40–80 times (depending on the fuel supply method) less than the increase in the chemical energy (compared to the case of no laser exposure) released due to fuel combustion.     

Is the Maxwell–Sillars–Wagner model reliable for describing the dielectric properties of a core–shell particle–epoxy system?

Dielectric measurements have been performed on neat acrylic core–shell particles, and core–shell modified-epoxy networks in order to assess the accuracy of the Maxwell–Wagner–Sillars (MWS) model in describing the dielectric properties of heterogeneous polymeric systems. Measured and predicted interfacial polarizations are compared. The temperature dependence of the frequency of maximum interfacial dielectric loss process is well described by the MWS model and from the temperature dependence of the conductivity of the two phases. However, the measured and predicted absolute values differ and a distribution in the interfacial relaxation time is observed. This is attributed to the effect of a gradient in concentration across the interface between the acrylic particles and the epoxy matrix. It is thus concluded that the nature and properties of interphases can strongly influence the dielectrical properties and interfacial polarization processes in polymer blends, and that theoretical models which do not take into account details of interfacial charge transfer might not be reliable in describing the morphology of heterogeneous polymeric systems.     

Effect of the design of a feedstock injection device in a fluidized-bed reactor on the efficiency of the reaction using the dehydrogenation of <Emphasis Type="Italic">iso</Emphasis>-paraffins in a fluidized chromia–alumina catalyst bed as an example

Mathematical modeling is performed for the operation of two units of industrial chemical fluidized-bed reactors with different gas feedstock injection devices, i.e, three toroidal rings with nozzles in unit 1 and a false bottom with nozzles distributed over it in unit 2. Efficiency is analyzed (using the target product (iso-butylene) yield) for the operation of the two units over 4 months under industrial conditions and revealed the higher efficiency of unit 2. To dedetrmine the reasons for different product yields in the two units, a numerical solution is found by mathematical modeling to obtain characteristic pictures of catalyst particle concentrations and temperature fields in these units. It is concluded that unit 2 is characterized by a more uniform and dense distribution of the catalyst along with more uniform heating of the reactor. Pictures of the principal catalyst circulation flows are plotted to explain the considerable difference between the catalyst concentrations and gas temperature fields. Based on the numerical solution, the operational efficiency of the two units is subjected to comparative analysis, which showed good agreement with the results from an analysis of industrial reactors. The approach used in this work could be used in designing new units and optimizing existing units.     

Production of an antimicrobial compound by <Emphasis Type=Italic>Bacillus subtilis</Emphasis> LS 1–2 using a citrus-processing byproduct

The aim of this study was to investigate the antimicrobial activity of Bacillus subtilis LS 1–2 grown on citrus juice waste (CJW). Citrus-juice waste (CJW) was obtained from the residue of squeezed citrus fruits. To use CJW as a raw material for the growth of B. sutilitis, a citrus-juice medium (CJM) was prepared by treating CJW with Ca(OH)₂. No antimicrobial activity was observed either in the culture broth of Luria Broth medium or in CJM itself. The maximum antimicrobial activity was obtained after 24 hr of cultivation (culture) of Bacillus sutilitis LS 1–2 in CJM. The culture supernatant exhibited inhibitory activity against E. coli O-157 (140 AU/mL), Staphylococcus aureus (180 AU/mL), and Candida albicans (260 AU/mL), respectively. Bacillus subtilus LS 1–2 also produced protease (3,600 U/ml) and amylase (290 U/ml) in CJM. Antimicrobial activity of the culture broth was stable for 1 hr at 100 °C, pH 2–10, and bile acid (concentration needs, 1 mM TDOC and 0.27 mM DOCmM), respectively. These results indicate the potential of CJW as a novel bioresource and the scope of probiotic applications of Bacillus subtilis LS 1–2 in various industrial applications.     

Pipe flow of a dense emulsion: Homogeneous shear‐thinning or shear‐induced migration?

The flow field of a 70% concentrated noncolloidal o/w emulsion in a pipe has been investigated by means of Particle Image Velocimetry in a matched refractive index medium. At steady state and in laminar regime, the shape of axial velocity profiles is not parabolic and exhibits a shear‐thinning behavior of the dense emulsion, with a flow index of 0.5 and a negligible yield stress (less than 1 Pa). However, instead of a square root law, the pressure drop increases linearly with U_m. To explain this apparent inconsistency, two mechanisms of different nature are considered. The first originates from a possible relation between the consistency factor and the drop mean diameter. The second mechanism is shear‐induced migration and leads to the development of a concentration gradient in the pipe cross section. Both mechanisms considered reconcile the experimental data, the apparent local shear‐thinning behavior and the linear evolution of the pressure drop with the flow rate. © 2017 American Institute of Chemical Engineers AIChE J, 2017     

Could Small Heat Shock Protein HSP27 Be a First-Line Target for Preventing Protein Aggregation in Parkinson’s Disease?

Small heat shock proteins (HSPs), such as HSP27, are ubiquitously expressed molecular chaperones and are essential for cellular homeostasis. The major functions of HSP27 include chaperoning misfolded or unfolded polypeptides and protecting cells from toxic stress. Dysregulation of stress proteins is associated with many human diseases including neurodegenerative diseases, such as Parkinson’s disease (PD). PD is characterized by the presence of aggregates of α-synuclein in the central and peripheral nervous system, which induces the degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and in the autonomic nervous system. Autonomic dysfunction is an important non-motor phenotype of PD, which includes cardiovascular dysregulation, among others. Nowadays, the therapies for PD focus on dopamine (DA) replacement. However, certain non-motor symptoms with a great impact on quality of life do not respond to dopaminergic drugs; therefore, the development and testing of new treatments for non-motor symptoms of PD remain a priority. Since small HSP27 was shown to prevent α-synuclein aggregation and cytotoxicity, this protein might constitute a suitable target to prevent or delay the motor and non-motor symptoms of PD. In the first part of our review, we focus on the cardiovascular dysregulation observed in PD patients. In the second part, we present data on the possible role of HSP27 in preventing the accumulation of amyloid fibrils and aggregated forms of α-synuclein. We also include our own studies, highlighting the possible protective cardiac effects induced by L-DOPA treatment through the enhancement of HSP27 levels and activity.