Theranostic Interpolation of Genomic Instability in Breast Cancer

Breast cancer is a diverse disease caused by mutations in multiple genes accompanying epigenetic aberrations of hazardous genes and protein pathways, which distress tumor-suppressor genes and the expression of oncogenes. Alteration in any of the several physiological mechanisms such as cell cycle checkpoints, DNA repair machinery, mitotic checkpoints, and telomere maintenance results in genomic instability. Theranostic has the potential to foretell and estimate therapy response, contributing a valuable opportunity to modify the ongoing treatments and has developed new treatment strategies in a personalized manner. “Omics” technologies play a key role while studying genomic instability in breast cancer, and broadly include various aspects of proteomics, genomics, metabolomics, and tumor grading. Certain computational techniques have been designed to facilitate the early diagnosis of cancer and predict disease-specific therapies, which can produce many effective results. Several diverse tools are used to investigate genomic instability and underlying mechanisms. The current review aimed to explore the genomic landscape, tumor heterogeneity, and possible mechanisms of genomic instability involved in initiating breast cancer. We also discuss the implications of computational biology regarding mutational and pathway analyses, identification of prognostic markers, and the development of strategies for precision medicine. We also review different technologies required for the investigation of genomic instability in breast cancer cells, including recent therapeutic and preventive advances in breast cancer.     

Physiologic Insulin Resensitization as a Treatment Modality for Insulin Resistance Pathophysiology

Prevalence of type 2 diabetes increased from 2.5% of the US population in 1990 to 10.5% in 2018. This creates a major public health problem, due to increases in long-term complications of diabetes, including neuropathy, retinopathy, nephropathy, skin ulcers, amputations, and atherosclerotic cardiovascular disease. In this review, we evaluated the scientific basis that supports the use of physiologic insulin resensitization. Insulin resistance is the primary cause of type 2 diabetes. Insulin resistance leads to increasing insulin secretion, leading to beta-cell exhaustion or burnout. This triggers a cascade leading to islet cell destruction and the long-term complications of type 2 diabetes. Concurrent with insulin resistance, the regular bursts of insulin from the pancreas become irregular. This has been treated by the precise administration of insulin more physiologically. There is consistent evidence that this treatment modality can reverse the diabetes-associated complications of neuropathy, diabetic ulcers, nephropathy, and retinopathy, and that it lowers HbA1c. In conclusion, physiologic insulin resensitization has a persuasive scientific basis, significant treatment potential, and likely cost benefits.     

Two new Protecting Groups for the Guanidino Function of arginine

Two new synthons, Fmoc-L-Arg(biphenyl-4-sulphonyl)-OH ( 8 ) and Fmoc-Arg(4-methoxy-3-t-butylbenzenesulphonyl)-OH ( 14 ), are prepared for the synthesis of arginine-containing peptides. These groups are cleaved by commonly employed trifluoroacetic acid and methanesulphonic acid. Kinetic studies reveal that extended bicyclic aromatic conjugation, as in biphenyl, slightly improves the acid lability compared to the electron-donating t-butyl group.     

LCZ696 Protects against Diabetic Cardiomyopathy-Induced Myocardial Inflammation,ER Stress,and Apoptosis through Inhibiting AGEs/NF-κB and PERK/CHOP Signaling Pathways

The present study is designed to determine the effect of LCZ696 on DCM in rats and investigate the underlying mechanism involved. Diabetes was induced by feeding rats with a high-fat diet for six weeks following a single injection of STZ (30 mg/kg). Diabetic rats were divided into three groups (n = 10). LCZ696 and valsartan treatment was started two weeks after diabetic induction and continued for eight weeks. At the end of the treatment, serum and cardiac tissues were analyzed by RT-PCR, Western blot, and ELISA kits. LCZ696 and valsartan ameliorated DCM progression by inhibiting AGEs formation at activity levels; pro-apoptotic markers (BAX/Bcl2 ratio and caspase-3) in mRNA and protein expressions, the NF-κB at mRNA; and protein levels associated with the restoration of elevated proinflammatory cytokines such as the TNF-α, IL-6, and IL-1β at the activity level. Furthermore, LCZ696 and valsartan contribute to restoring the induction of ER stress parameters (GRP78, PERK, eIF2a, ATF4, and CHOP) at mRNA and protein levels. LCZ696 and valsartan attenuated DCM by inhibiting the myocardial inflammation, ER stress, and apoptosis through AGEs/NF-κB and PERK/CHOP signaling cascades. Collectively, the present results reveal that LCZ696 had a more protective solid effect against DCM than valsartan.     

Antioxidant capacity and total phenolics of <Emphasis Type="Italic">Cyphostemma digitatum</Emphasis> before and after processing: use of different assays

In the framework of standardisation of new healthy food sources, this paper aimed to study the total phenolics and the antioxidant power of Cyphostemma digitatum (Vitaceae) in water and ethanol extracts, using 96-well micro plates with BMG FLUOstar Optima micro plate reader. Total phenolics by Folin–Ciocalteu method in the water extracts were significantly lower after processing, decreasing from 1.41 ± 0.06 g GAE/100 g in the raw leaves to 0.80 ± 0.08 g GAE/100 g in the processed sample; the ethanol extract revealed the same trend with higher values, decreasing from 1.95 ± 0.03 to 1.56 ± 0.12 g GAE/100 g. The antioxidant capacity was elucidated by four methods: TEAC, DPPH, FRAP and ORAC. No or very weak correlations were found between antioxidant assays and total phenolics; this confirms that the antioxidant capacity could be attributed to other molecules. The ORAC assay proved to be more powerful than the other assays; it showed 103.3 ± 2.5 mmol/100 g Trolox equivalents in the raw leaves ethanol extract and 91.9 ± 3.0 mmol/100 g in the processed sample. ORAC assay showed the opposite for the water extract where the antioxidant capacity increased from 16.7 ± 0.2 to 41.7 ± 2.7 mmol/100 g Trolox equivalents after processing, which could be attributed to new water-soluble compounds generated in the consumed form.     

Underground coal gasification: A new clean coal utilization technique for India

Energy demand of India is continuously increasing. Coal is the major fossil fuel in India and continues to play a pivotal role in the energy sector. India has relatively large reserves of coal (253 billion tonnes) compared to crude oil (728 million tonnes) and natural gas (686 billion cubic meters). Coal meets about 60% of the commercial energy needs and about 70% of the electricity produced in India comes from coal, and therefore there is a need for technologies for utilization of coals efficiently and cleanly. UCG offers many advantages over the conventional mining and gasification process. UCG is a well proven technology. Due to the site-specific nature of the process, possibility of land subsidence and surrounding aquifer water contamination, this technology is still in a developing stage in India. Potential for UCG in India is studied by comparing the properties of Indian coals with the properties of coal that are utilized by various UCG trials. The essential issues are elaborated for starting UCG in India based on the reported information from the successful field trials conducted all over the world. Indian industries are in the process of initiating pilot studies of UCG at various sites. This study will help to motivate both applied and theoretical research work on UCG sites in India and after detailed analysis it will provide basic data to interested industries.     

Concentrator silicon solar cells from silicon industry rejects

Two types of silicon (Si) substrates (40 n-type with uniform base doping and 40 n/n⁺ epitaxial wafers) from the silicon industry rejects were chosen as the starting material for low-cost concentrator solar cells. They were divided into four groups, each consisting of 20 substrates: 10 are n/n⁺ and 10 are n substrates, and the solar cells were prepared for different diffusion times (45, 60, 75 and 90 min). The fabricated solar cells on n/n⁺ substrates (prepared with a diffusion time of 75 min) showed better parameters. In order to improve their performances, particularly the fill factor, 20 new solar cells on n/n⁺ substrates were fabricated using the same procedure (the diffusion time was 75 min)—but with four new front contact patterns. Investigation of current–voltage (I–V) characteristics under AM 1.5 showed that the parameters of these 20 new solar cells have improved in comparison to previous solar cells' parameters, and were as follows: open-circuit voltage (V_OC=0.57 V); short circuit current (I_SC=910 mA), and efficiency (η=9.1%). Their fill factor has increased about 33%. The I–V characteristics of these solar cells were also investigated under different concentration ratios (X), and they exhibited the following parameters (under X=100 suns): V_OC=0.62 V and I_SC=36 A.     

Natural Convection of Nanofluid in Cylindrical Enclosure Filled with Porous Media

A numerical study has been carried out to investigate the effect of aspect ratio on heat transfer by natural convection of nanofluid taking Cu nano particles and the water as based fluid. The flow is laminar, steady state, axisymmetric two-dimensional in a vertical cylindrical channel filled with porous media. Heat is generated uniformly along the center of the channel with its vertical surface remain with cooled constant wall temperature and insulated horizontal top and bottom surfaces. The governing equations which used are continuity, momentum and energy equations using Darcy law and Boussinesq＇s approximation which are transformed to dimensionless equations. The finite difference approach is used to obtain all the computational results using the MATLAB-7 program. The parameters affected on the system are Rayleigh number ranging within （10≤ Ra ≤ 103）, aspect ratio （1 ≤ As 〈 5） and the volume fraction （0 ≤0 〈 0.2）. The results obtained are presented graphically in the form of streamline and isotherm contour plots and the results show that as ~ increase from 0.01 to 0.2 the value of the mean Nusselt number increase 50.4% for Ra = 1,000.     

Direct Synthesis of Pyrazoles via reaction of C-ethoxycarbonyl-N-arylnitrilimines with benzalmalononitriles and some α-cyanocinnamic acid derivatives

Reaction of C-ethoxycarbonyl-N-arylnitrilimines ( 2a–d ) with α, β-disubstituted acrylonitriles ( 3a–f ) in refluxing benzene affords the corresponding substituted pyrazoles 5a–f and 6a–c respectively in good yield. However, reaction of 2a–e with 3g gives the 2-pyrazoline derivatives 7a–d . The assigned structures for the products 5–7 were confirmed by their spectra (i.r., ¹H-n.m.r.) and elemental analyses. Also the structures of the pyrazoles 5 were substantiated by comparison with their regioisomeres 8 .     

Zur Reaktion von N-Aryl-2,4-dimethyl-buta-1,3-dien-1,4-sultamen mit Tetracyanethylen; 1H-, 13C- und 15N-spektroskopische Charakterisierung der Tetracyan-ethylierungs- und Tricyan-vinylierungsprodukte

About the Reaction of N-Aryl-2,4-dimethyl-buta-1,3-dien-1,4-sultames with Tetracyanoethylene; ¹H, ¹³C and ¹⁵N N.M.R. Spectroscopic Charcterization of the Products of Tetracyanethylation and Tricyanvinylation The 4-methyl group in N-aryl-2, 4-dimethyl-buta-1,3-dien-1, 4 sultames is C H-acidic and adds therefore to tetracyanethylene. The adducts easily lose HCN on dissolving in DMSO to form N-aryl-2-methyl-4-(2, 3, 3-tricyanoprop-2-ene-1-ylidene)-but-2-en-1, 4-sultames 4 , which form sodium salts at C-1. The structures of the compounds obtained were determined by ¹³C and ¹⁵N n.m.r. spectroscopy.