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Mechanisms of Resistance to Kinase Inhibitors and Strategies to Prevent the Development of Drug Resistance

Targeting mutant proteins and associated signaling pathways of driver oncogenes by small molecule kinase inhibitors (KIs) are a promising strategy of cancer therapy. However, despite the initial success of treatment, KIs often become ineffective as intrinsic and acquired resistance. This article reviews the English-language literature to explore the underlying mechanisms of drug resistance and to present a challenge for developing drugs to overcome resistance. Mechanisms of acquired resistance include 1) the selection of pre-existing subclones with other mutations, 2) the emergence of secondary mutations in the target kinase domain, 3) upregulation of kinases both within the same kinase family and their related kinase families, as well as activation of alternative bypass pathways, 4) epithelial-mesenchymal transition, 5) overexpression of pro-survival Bcl-2 family proteins and 6) drug efflux mechanisms. Currently available methods are to obtain tumor biopsy samples at recurrence or progression if the tumor lesion is accessible to a biopsy and to use the second- and third-generation KIs based on the individual need of each patient. Furthermore, recent computational challenges provide design principles to prevent the development of drug resistance. In conclusion, we provide an overview of the postulated resistance mechanisms and highlight the future direction of computational structure-based design of new potent KIs.
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Heavy Element Accumulation in Aquatic Beetles of the Genus Enochrus (Coleoptera: Hydrophilidae) in Erzurum Province

In the present study, fourteen heavy elements (Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Se, Br, Sr, Pb) accumulation in sediment, water and Enochrus spp. species organs (total body) were evaluated. For this purpose, water, sediment and Enochrus spp. were collected from nine wetland sites in Erzurum province (Turkey).
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The Human –Cat Relationship, Myths/Superstitions and its Consequences on Cat Ownership in Maiduguri, Northeastern Nigeria

A survey was designed to determine the human-cat relationship, myths/superstition and its consequences on cat ownership in Maiduguri, Nigeria. Close ended structured questionnaires were administered to 200 households randomly selected from four wards in Maiduguri. The response rate was 98.0%. Out of the 200 households, 196 (98.0%) participated, while 4 (2.0%) did not. Of the 196 households that took part in the survey, 168 (84.0%) owned cats while 28 (14.0%) did not. A total of 310 cats were owned by the 168 participating households. Elderly women owned 55.5% of the cats, while children and young ladies owned 35.0% and 3.5% respectively. Only 1 cat was neutered, while the remaining 309 (99.7%) were intact. The cats were kept for the purpose of companionship and rodent control. All the cats were of non-specific breed and had never been vaccinated against any specific disease(s). Some cat owners in Maiduguri believed in myths/superstitions associated with the domestic house cat. However, it was concluded that households in Maiduguri viewed keeping cats positively but did not provide the expected housing, feeding and medications as practiced in more advanced countries.
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A New Mechanism of the Nanoindentation Process

A new mechanism of the nanoindentation process based on the consideration of the decrease the energy of the chemical bonds as a result of the pressure of the indenter on the material is proposed. This leads to an increase the mobility of the atoms, which in the beginning creates point defects and as the external force increases, melting and material destruction occurs.
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Labetalol in Comparison to Methyl Dopa in Treatment of Gestational Hypertension, A Randomized Trial

To evaluate the value and safety of labetalol in comparison to Alfa methyldopa in treatment of pregnant women with pregnancy-induced hypertension (PIH). 264 patients with PIH were randomly distributed to take either methyldopa (group 1) labetalol (group 2). or Intake of medications with respect to Age, gravidity, Blood Pressure measurement, albumin in urine measurement Levels, Side Effects, dose of the drug, increasing duration of pregnancy, mode of delivery, Perinatal safety and APGAR scores were studied. The statistical level of significance was taken at P<0.05.
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The Development of the Prognostat Tool for Survival Prediction in Palliative Care Patients

Since a common question arises toward the end of life about prognosis and that clinicians vary widely in the accuracy of their survival predictions, it is important that advancements be developed, one of which is to design or improve prognostic tools. To test the reliability of the new Prognostat tool for survival. Prospective multi-site mixed methods study with data collection, survey, and focus groups. prediction in palliative care patients. Prognostat form completed during first assessment by a palliative physician or nurse on admission to a palliative care unit or first ward or home consult.
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Malignant Soft Tissue Sarcoma at the Site of Corticosteroid Injection in a Dog

An 11-year-old spayed female dog was presented for a large mass on the left proximal pelvic limb. The mass appeared three months prior to presentation in the location of a previous corticosteroid injection, Kenalog (0.05 mg/kg triamcinolone, CAS# 76-25-5). No vaccinations or injections had been previously given in this area. The mass spanned from the left stifle to the coxofemoral joint and was firm, circular, non-moveable, and diffusely mixed within the musculature of the thigh. A left external complete hemipelvectomy was performed. Histopathology was consistent with a Grade III fibromyxosarcoma. The dog died naturally at home five months after surgery. This is the first account of association of a corticosteroid injection with formation of a fibromyxosarcoma in a dog.
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Tracing Echinococcosis in Portugal - The Role of the Abattoirs in North Douro Region

The occurrence of cystic echinococcosis (CE) at a national level or in large regional areas is an issue difficult to determine in a cost-effective way, integrating both human and animal data, and thus leading to effective control measures. In Portugal, the abattoirs in north Douro region receive a large percentage of heads of cattle from the whole country which makes them ideal places for the implementation of a surveillance system for this zoonosis. Data was obtained for cattle slaughtered in 9 abattoirs in north region of Douro River, with visible CE-like cysts at meat inspection. An excel database was constructed with the records of condemned viscera due to hydatid cysts in cattle for 2008, 2009, 2010, and the first half of 2011. Most of the cysts were found in the lungs and livers (23.5%), only in livers (21.5%) or only in lungs (18.1%). Individual information concerning each animal contributed to the depiction of a distribution map by regions of the occurrence of positive cases in Portugal. From the 149 cases registered, it was possible to identify the place of infection in 93 cases (62.4%), in which the rate of distribution was 21 (22.6%) in the north, 14 (15.1%) in the center, 57 (61.3%) in Alentejo and 1 case (1.1%) in Algarve. This distribution of cases coincides with the location of human and animal cases reported before, with special focus on the Alentejo and in the northeast of the country.
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An Application: Representations of Some Systems on Non-Deterministic EEG Signals

In this paper, we introduce the notion of a complex interval which is significant for interval-valued data and interval-based signal processing. First, we present the space of complex intervals and investigate the quasilinear structure of the space of complex intervals. We observe that this space is Hilbert quasilinear space with a set-valued inner product.
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Metaphysical Analysis of the Nutritional and Therapeutic Value of Baobab (Adansonia Digitata L.)

Realistic assessment of the yield and nutritional value of baobab as well as the elucidation of its inhibitory action against oxidative stress were the targets of the study. An average baobab tree can yield 80kg fruits, 14kg pulp, 23kg seeds and 130kg leaves per year. Despite considerable variability, the leaves outstrip in mean Ca (1241 mg/100g dry sample), Fe (40mg/100g dry sample) and ß-carotene (135μg/100g dry sample) content.
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Magnetic Moment of Zigzag CuO Nanotubes at Different Temperature and Size: Ab-Initio Study

Temperature and size dependence magnetic moment of zigzag (n, 0) (n= 4, 6, 8, 10) copper oxide nanotubes (CuO NTs) have been computed by using a standard density functional theory. The computational work carried out by employing spin polarized generalized gradient approximation with revised Perdew Burke Ernzerhoff type parameterization along ab-initio approach. Bond length, binding energy and total magnetic moment have been analyzed and found that the bond length decreases at first and become saturated with increasing size of the nanotube.
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Two-Dimensional Infrared Correlation Spectroscopy, Linear Two-Dimensional Infrared Spectroscopy and Non-Linear Two-Dimensional Infrared Spectroscopy Comparative Study on Malignant and Benign Human Cancer Cells and Tissues under Synchrotron Radiation with the Passage of Time

In the current study, we have experimentally and comparatively investigated and compared malignant human cancer cells and tissues before and after irradiating of synchrotron radiation using Two-Dimensional Infrared Correlation Spectroscopy, Linear Two-Dimensional Infrared Spectroscopy and Non-Linear Two-Dimensional Infrared Spectroscopy.
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Cell Culture, Cytopathic Effect and Immunofluorescence Diagnosis of Viral Infection

Viruses are obligate intracellular parasites that require living cells in order to replicate. Cell culture for propagation and identification of viruses is an important component of the clinical virology laboratory. In general, diagnostic tests can be grouped into three categories: direct detection, virus isolation and serology. Direct examination methods can usually give a result either within the same or the next day. Immunofluorescence is widely used for the rapid diagnosis of virus infections by detection of virus antigen in clinical specimens and detection of virus-specific antibodies.
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Dietary Intake, Anthropometric Characteristics and Clinical Assessment of Elderly in Ondo State, Nigeria

This study was designed to assess the nutrition status of the elderly in Ondo State Nigeria. Random sampling techniques were used to select 1155 elderly for this study. Socio-demographic characteristics, clinical assessment, food consumption pattern, anthropometric measurements of the elderly were determined. Data entry and analysis were done with the use of scientific instruments. This involved the SPSS version 17. It detailed the analytical tools, including frequencies, percentage and correlations. The result showed that Intake of nutrients by the elderly was shown to be inadequate.
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Protocol for Root Canals’ Irrigation in Endodontic Practice in Ivory Coast: A Survey of 100 Dentists

In endodontics, a chemo-mechanical preparation is used to disinfect the root canal system. However, due to limitations of endodontic devices, which shape the main canal, this preparation is supplemented by irrigation solutions. In Ivory Coast, late consultations and advanced stages of pathologies characterized the endodontics.
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Ordered Growth of Anodic Aluminum Oxide in Galvanostatic and Galvanostatic-Potentiostatic Modes

The results are presented of obtaining anodic aluminum oxide with an ordered pore arrangement by employing two anodizing modes - galvanostatic mode and combined (galvanostatic + potentiostatic) mode, at high values of the current density and voltage. Use has been made of an oxalate electrolyte and a complex electrolyte comprising oxalic acid and phosphoric acid. Scanning electron microscopy has been used to investigate the surface morphology of the barrier and porous layers and to determine pore sizes and inter-pore distance.
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Anodizing for Design and Function

Two basic reactions occur during the anodizing of aluminum: 1) the aluminum is consumed and 2) an oxide grows. By accepting this statement as true, the anodizing process can be viewed as a corrosion process, and anodizing can be modeled using the Tafel Equation. Anodizing process parameters of electrolyte chemistry and concentration, temperature, aluminum substrate resistance and current density are presented as they relate to the Tafel Equation and how they impact the anodic aluminum oxide structure and properties. Understanding this relationship is consequent in making anodizing an engineering process, one that enables tuning the structure such that it yields distinct characteristics to fulfill design and application requirements.
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Recent Developments in Human Odor Detection Technologies

Human odor detection technologies have drawn attention due to the wide possibility of potential applications they open up in areas such as biometrics, criminal investigation and forensics, search for survivors under rubble, and security checkpoint screening. Gas chromatography/mass spectrometry (GC/MS) has been the most successful and powerful analytical approach developed to date for human odor analysis, and hundreds of human odorants have been identified using this tool.
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Electronic-nose Applications in Forensic Science and for Analysis of Volatile Biomarkers in the Human Breath

The application of electronic-nose (E-nose) technologies in forensic science is a recent new development following a long history of progress in the development of diverse applications in the related biomedical and pharmaceutical fields. Data from forensic analyses must satisfy the needs and requirements of both the scientific and legal communities. The type of data collected from electronic-nose devices provides a means of identifying specific types of information about the chemical nature of evidentiary objects and samples under investigation using aroma signature profiles of complex gaseous mixtures containing volatile organic compounds (VOCs) released from manufactured products and parts of the human body. E-nose analyses also provide useful qualitative information about the physicochemical characteristics and metabolic conditions of human subjects without the need for time-consuming analyses to identify all chemical components in human-derived volatile mixtures.
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Analysis of Sweat Simulant Mixtures using Multiplexed Arrays of DNA-Carbon Nanotube Vapor Sensors

Carbon nanotube (NT) based electronic vapor sensors were tested against synthetic sweat solutions, consisting of 13 volatile organic compounds (VOCs) in saline, in order to probe the device ability to analyze and differentiate vapors derived from complex biological samples.
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Characteristic Human Scent Compounds Trapped on Natural and Synthetic Fabrics as analyzed by SPME-GC/MS

The collection of human odor volatiles is of interest to forensic applications as a path to investigate canine scent discriminations in legal investigations. A study using a selected array of previously identified human odor compounds has been conducted to determine the retention and release capabilities of five (5) natural and synthetic fabric types, cotton (mercerized fabric and gauze matrix), polyester, rayon and wool.
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The Effects of the Film Thickness and Roughness in the Anodization Process of Very Thin Aluminum Films

The anodization of aluminum foils having micrometer thickness is a common process and results in hexagonally self-ordered alumina membranes. However, anodic aluminum oxide (AAO) membranes fabricated from nanometer-thin films present new challenges to the anodization process, since aluminum films adheres poorly on supporting substrates and the smoothness of the film is highly related to the kind of substrate.
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Anodic Oxidation of Titanium in Sulphuric Acid and Phosphoric Acid Electrolytes

Anodisation of pure titanium has been carried out in sulphuric and in phosphoric acid solutions at potentials ranging from 50 to 150V. The SEM and AFM morphological analysis indicates that, within this potential range, oxidation in sulphuric acid solution produces better developed mesoporous oxide layers.
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Fabrication of Ordered Arrays of Anodic Aluminum Oxide Pores with Interpore Distance Smaller than the Pitch of Nano-pits formed by Ion Beam Etching

We investigated a method for preparation of ordered nanopore arrays with the interpore distance of 60 nm by guided self-organization of anodic aluminum oxide with a prepatterned array of pits in the starting Al film.
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Preparation of Large Area Anodic Alumina Membranes and their Application to Thin Film Fuel Cell

The design of an electrochemical reactor for the preparation of self-supported comparatively thin (up to 10 μm) and large area (up to 50 cm2) anodic alumina membranes is described allowing growth of porous alumina at high applied potential (up to 150 V) without burning.
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Fabrication of Vertical Cu2ZnSnS4 Nanowire Arrays by Two-Step Electroplating Method into Anodic Aluminum Oxide Template

Vertical Cu2ZnSnS4 (CZTS) nanowire arrays have been synthesized via two-step electroplating method into anodized aluminum oxide template. For deposition of CZTS nanowires, anodized aluminum oxide (AAO) was used as the growth mask for the growth of the nanowires. AAO templates with hole sizes of 70 nm in diameter were used in the experiments.
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Fabrication and Luminescence of Anodic Alumina with Incorporated Vanadyl Citrate Chelate Anions

Anodic aluminum oxide doped with vanadyl citrate chelate complex anions was formed by a two-step self-organized anodization in 2 wt. % sulfuric acid containing 0.04 M V2O5 and 0.08 M citric acid at voltage range 13-23 V, and at 0 and 15 oC. The combination of two temperatures and at least four voltages (depending on the applied temperature) was applied as the operating conditions of anodization.
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Synthesis of BaTiO3 Nanowires via Anodic Aluminum Oxide Template Method Assisted by Vacuum-and-Drop Loading

In this paper, we report on the synthesis of BaTiO3 nanowires via the anodic aluminum oxide template method. To fill in the precursors of BaTiO3 into anodic aluminum oxide templates, the vacuum and drop loading method developed in our previous study was used. Ba(CH3COO)2 (barium acetate) and C12H28O4Ti (tetraisopropyl orthotitanate) were used as Ba and Ti sources, respectively. Anodic aluminum oxide membranes with the through-hole diameter of ~200 nm were used as the template for BaTiO3 nanowires.
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Editorial Board Members Related to TIC

Kornélia Tekes

Department of pharmacodynamics
Semmelweis University

Mehdi Rahimi

Assistant Professor
Department of Biotechnology
Institute of Science and High Technology and Environmental Sciences

Roger M. Loria

Department of Microbiology and Immunology
Virginia Commonwealth University
United States


Associate Professor
Center of Biomolecular Therapeutics
University of Maryland
United States

Ch. Niranjan Patra

Department of Pharmaceutics
Roland Institute of Pharmaceutical sciences

Bryan Krantz

Associate professor
Department of Microbial Pathogenesis
University of Maryland
United States

Arunima Mukhopadhyay

Research assistant
Paul O'Gorman Leukaemia Research Centre
University of Glasgow
United Kingdom

Jean Carlet

World Alliance Against Antibiotic Resistance (WAAAR)

Hyunjin Park

Associate Professor
School of Electronic Electrical Engineering
Sungkyunkwan University

Tamer Atif Mohamed Dawod

Associate Professor
Faculty of Medicine
Mansoura University
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