On fundamental group of Riemannian manifolds with ommited fractal subsets

We show that if K is a closed and bounded subset of a Riemannian manifold M of dimension m>3, and the fractal dimension of K is less than m−3, then the fundamental groups of M and M−K are isomorphic.Показано, що якщо K — замкнена й обмежена пiдмножина рiманового многовиду M розмiрностi m>3, а фрактальна розмiрнiсть K менша за m−3, то фундаментальнi групи M i M−K є iзоморфними

The effect of green chemistry education based on practical activity on learning and attitude of pre-service chemistry teachers

Background and Objective:Chemistry plays a fundamental role in human civilization and its place in economics, politics and life is becoming more and more prominent and covers a wide range of chemical products such as drugs, dyes, fertilizers, etc. However, the environmental damage caused by it is a major human concern. Many of us today take steps to reduce environmental impact, for example by participating in chemical recycling programs and using energy-saving light bulbs; we buy local products and maybe drive hybrid cars. But what if "we could somehow prevent pollution from the start?" Thus, with a new approach called green chemistry, chemists are being led to a new phase of research activities to develop green reactions and use them instead of the old methods, to help human health and society by eliminating toxins from chemical processes. The purpose of this research is education of green chemistry through the curriculum related to the principles of green chemistry in General Chemistry Lab 1and the effect of this educational course on learning and attitude of the pre-service chemistry teachers toward green chemistry principles. Methods: This educational course involves two green experiments implemented according to green chemistry principles. The experiments include determination of molar mass relation in a chemical reaction and determination of the amount of ascorbic acid in a tablet of vitamin C. The research methods are practical, experimental and quasi-experimental and the used instruments were the researcher-constructed tests in the field of learning and attitude domain. Statistic population of this study consists of experimental group (N=30) and control group (N=30) of the student teachers at Shahid Rajaee Teacher Training University in the academic year 2017-2018. Data analysis was done using descriptive and inferential statistics with SPSS software. Findings: The obtained results show that among12 principles of Green Chemistry, students have learned the principles of 1 to 4 and 7 to 12 of these 12 principles and they have been attracted to them. In addition, the implementation of a curriculum related to the principles of green chemistry has had a positive impact on the attitude of the pre-service chemistry teachers. Conclusion: Findings from the research show that teaching the principles of green chemistry can be done based on the activity-oriented approach in the chemistry curriculum as in most developed countries. Student-teacher education can lead them to develop a positive attitude towards green chemistry and to have more motivation and desire to study chemistry based on the principles of green chemistry and to pass this attitude on to their students in the teaching process. Also, in designing the curriculum, it should be noted that in the sequence of practical activities, it should be done in such a way that it includes all the principles of green chemistry so that education based on it can give all the principles of green chemistry to learners or give them a positive attitude.   ===================================================================================== COPYRIGHTS  ©2019 The author(s). This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, as long as the original authors and source are cited. No permission is required from the authors or the publishers.  ====================================================================================

Tectono-stratigraphic evolution of the intermontane Tarom Basin (NW sectors of the Arabia-Eurasia collision zone): insights into the vertical growth of the Iranian Plateau margin

The intermontane Tarom Basin of NW Iran (Arabia-Eurasia collision zone) is located at the transition between the Iranian Plateau (IP) to the SW and the Alborz Mountains to the NE. This basin was filled by Late Cenozoic synorogenic red beds that retain first-order information on the erosional history of adjacent topography, the vertical growth of the plateau margin and its lateral (orogen perpendicular) expansion. Here, we perform a multidisciplinary study including magnetostratigraphy, sedimentology, geochronology and sandstone petrography on these red beds. Our data show that widespread Eocene arc volcanism in NW Iran terminated at ~ 38-36 Ma, while intrabasinal synorogenic sedimentation occurred between ~ 16.5 and < 7.6 Ma, implying that the red beds are stratigraphically equivalent to the Upper Red Formation. After 7.6 Ma, the basin experienced intrabasinal deformation, uplift and erosion in association with the establishment of external drainage. Fluvial connectivity with the Caspian Sea, however, was interrupted by at least four episodes of basin aggradation. During endorheic conditions the basin fill did not reach the elevation of the plateau interior and hence the Tarom Basin was never integrated into the plateau realm. Furthermore, our provenance data indicate that the northern margin of the basin experienced a greater magnitude of deformation and exhumation than the southern one (IP margin). This agrees with recent Moho depth estimates, suggesting that crustal shortening and thickening cannot be responsible for the vertical growth of the northern margin of the IP, and hence surface uplift must have been driven by deep-seated processes

Tectono-stratigraphic evolution of the intermontane Tarom Basin (NW sectors of the Arabia-Eurasia collision zone): insights into the vertical growth of the Iranian Plateau margin

The intermontane Tarom Basin of NW Iran (Arabia-Eurasia collision zone) is located at the transition between the Iranian Plateau (IP) to the SW and the Alborz Mountains to the NE. This basin was filled by Late Cenozoic synorogenic red beds that retain first-order information on the erosional history of adjacent topography, the vertical growth of the plateau margin and its lateral (orogen perpendicular) expansion. Here, we perform a multidisciplinary study including magnetostratigraphy, sedimentology, geochronology and sandstone petrography on these red beds. Our data show that widespread Eocene arc volcanism in NW Iran terminated at ~ 38-36 Ma, while intrabasinal synorogenic sedimentation occurred between ~ 16.5 and < 7.6 Ma, implying that the red beds are stratigraphically equivalent to the Upper Red Formation. After 7.6 Ma, the basin experienced intrabasinal deformation, uplift and erosion in association with the establishment of external drainage. Fluvial connectivity with the Caspian Sea, however, was interrupted by at least four episodes of basin aggradation. During endorheic conditions the basin fill did not reach the elevation of the plateau interior and hence the Tarom Basin was never integrated into the plateau realm. Furthermore, our provenance data indicate that the northern margin of the basin experienced a greater magnitude of deformation and exhumation than the southern one (IP margin). This agrees with recent Moho depth estimates, suggesting that crustal shortening and thickening cannot be responsible for the vertical growth of the northern margin of the IP, and hence surface uplift must have been driven by deep-seated processes

Analysis of radiation-induced cell death in head and neck squamous cell carcinoma and rat liver maintained in microfluidic devices

Objective The aim of this study was to investigate how head and neck squamous cell carcinoma (HNSCC) tissue biopsies maintained in a pseudo in vivo environment within a bespoke microfluidic device respond to radiation treatment. Study Design Feasibility study. Setting Tertiary referral center. Subjects and Methods Thirty-five patients with HNSCC were recruited, and liver tissue from 5 Wistar rats was obtained. A microfluidic device was used to maintain the tissue biopsy samples in a viable state. Rat liver was used to optimize the methodology. HNSCC was obtained from patients with T1-T3 laryngeal or oropharyngeal SCC; N1-N2 metastatic cervical lymph nodes were also obtained. Irradiation consisted of single doses of between 2 Gy and 40 Gy and a fractionated course of 5×2 Gy. Cell death was assessed in the tissue effluent using the soluble markers lactate dehydrogenase (LDH) and cytochrome c and in the tissue by immunohistochemical detection of cleaved cytokeratin18 (M30 antibody). Results A significant surge in LDH release was demonstrated in the rat liver after a single dose of 20 Gy; in HNSCC, it was seen after 40 Gy compared with the control. There was no significant difference in cytochrome c release after 5 Gy or 10 Gy. M30 demonstrated a dose-dependent increase in apoptotic index for a given increase in single-dose radiotherapy. There was a significant increase in apoptotic index between 1×2 Gy and 5×2 Gy. Conclusion M30 is a superior method compared with soluble markers in detecting low-dose radiation-induced cell death. This microfluidic technique can be used to assess radiation-induced cell death in HNSCC and therefore has the potential to be used to predict radiation response

New FTY720-docetaxel nanoparticle therapy overcomes FTY720-induced lymphopenia and inhibits metastatic breast tumour growth

Purpose: Combining molecular therapies with chemotherapy may offer an improved clinical outcome for chemoresistant tumours. Sphingosine-1-phosphate (S1P) receptor antagonist and sphingosine kinase 1 (SK1) inhibitor FTY720 (FTY) has promising anticancer properties, however, it causes systemic lymphopenia which impairs its use in cancer patients. In this study, we developed a nanoparticle (NP) combining docetaxel (DTX) and FTY for enhanced anticancer effect, targeted tumour delivery and reduced systemic toxicity. Methods: Docetaxel, FTY and glucosamine were covalently conjugated to poly(lactic-co-glycolic acid) (PLGA). NPs were characterised by dynamic light scattering and electron microscopy. The cellular uptake, cytotoxicity and in vivo antitumor efficacy of CNPs were evaluated. Results: We show for the first time that in triple negative breast cancer cells FTY provides chemosensitisation to DTX, allowing a four-fold reduction in the effective dose. We have encapsulated both drugs in PLGA complex NPs (CNPs), with narrow size distribution of ~ 100 nm and excellent cancer cell uptake providing sequential, sustained release of FTY and DTX. In triple negative breast cancer cells and mouse breast cancer models, CNPs had similar efficacy to systemic free therapies, but allowed an effective drug dose reduction. Application of CNPs has significantly reversed chemotherapy side effects such as weight loss, liver toxicity and, most notably, lymphopenia. Conclusions: We show for the first time the DTX chemosensitising effects of FTY in triple negative breast cancer. We further demonstrate that encapsulation of free drugs in CNPs can improve targeting, provide low off-target toxicity and most importantly reduce FTY-induced lymphopenia, offering potential therapeutic use of FTY in clinical cancer treatment

An insight to HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) pathogenesis; evidence from high-throughput data integration and meta-analysis

Background Human T-lymphotropic virus 1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a progressive disease of the central nervous system that significantly affected spinal cord, nevertheless, the pathogenesis pathway and reliable biomarkers have not been well determined. This study aimed to employ high throughput meta-analysis to find major genes that are possibly involved in the pathogenesis of HAM/TSP. Results High-throughput statistical analyses identified 832, 49, and 22 differentially expressed genes for normal vs. ACs, normal vs. HAM/TSP, and ACs vs. HAM/TSP groups, respectively. The protein-protein interactions between DEGs were identified in STRING and further network analyses highlighted 24 and 6 hub genes for normal vs. HAM/TSP and ACs vs. HAM/TSP groups, respectively. Moreover, four biologically meaningful modules including 251 genes were identified for normal vs. ACs. Biological network analyses indicated the involvement of hub genes in many vital pathways like JAK-STAT signaling pathway, interferon, Interleukins, and immune pathways in the normal vs. HAM/TSP group and Metabolism of RNA, Viral mRNA Translation, Human T cell leukemia virus 1 infection, and Cell cycle in the normal vs. ACs group. Moreover, three major genes including STAT1, TAP1, and PSMB8 were identified by network analysis. Real-time PCR revealed the meaningful down-regulation of STAT1 in HAM/TSP samples than AC and normal samples (P = 0.01 and P = 0.02, respectively), up-regulation of PSMB8 in HAM/TSP samples than AC and normal samples (P = 0.04 and P = 0.01, respectively), and down-regulation of TAP1 in HAM/TSP samples than those in AC and normal samples (P = 0.008 and P = 0.02, respectively). No significant difference was found among three groups in terms of the percentage of T helper and cytotoxic T lymphocytes (P = 0.55 and P = 0.12). Conclusions High-throughput data integration disclosed novel hub genes involved in important pathways in virus infection and immune systems. The comprehensive studies are needed to improve our knowledge about the pathogenesis pathways and also biomarkers of complex diseases.Peer reviewe

Trends in template/fragment-free protein structure prediction

Predicting the structure of a protein from its amino acid sequence is a long-standing unsolved problem in computational biology. Its solution would be of both fundamental and practical importance as the gap between the number of known sequences and the number of experimentally solved structures widens rapidly. Currently, the most successful approaches are based on fragment/template reassembly. Lacking progress in template-free structure prediction calls for novel ideas and approaches. This article reviews trends in the development of physical and specific knowledge-based energy functions as well as sampling techniques for fragment-free structure prediction. Recent physical- and knowledge-based studies demonstrated that it is possible to sample and predict highly accurate protein structures without borrowing native fragments from known protein structures. These emerging approaches with fully flexible sampling have the potential to move the field forward