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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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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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Empowering Key Populations (Kps) to Effectively Demand for Equal HIV/AIDS Services

AGHA in partnership with THETA and MNL with funding from CDC is implementing a Local Capacity Initiative project aimed at building capacity of CSOs working with KPs in Mukono, Kampala and Wakiso to advocate for improved HIV services. In Uganda, HIV prevalence among the general population stands at an average of 7.3% while among SWs is 35-37% and MSM at 13.7% between the age of 18-24.Over 40-50% of the new infections come from KPs (UAC, HIV /AIDS Indicator survey 2011). Programs targeting KPs continue to be characterized by limited coverage, poorly linked care, treatment and referral services. The project has increased capacity of 15 CSOs to demand accountability from government on national commitments on KPs; increased capacity of KPs to identify the legal and policy framework that impede equitable access, increased participation and representation of community leaders and KPs living with HIV in the governance structures that influence health services delivery.
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Relationship of YWHAH Single Nucleotide Polymorphisms to Markers of Rheumatoid Arthritis Disease Severity

Introduction: Serum 14-3-3 eta provides diagnostic and prognostic information in Rheumatoid Arthritis (RA). It is coded by the YWHAH gene with single nucleotide polymorphisms (SNPs) linked to bipolar disorder and schizophrenia. It was hypothesized that 6 previously described YWHAH SNPs might relate to markers of RA disease severity such as seropositivity or erosive changes. Association study performed at an academic hospital Rheumatology Clinic. Subjects studied were 18 years of age or older with RA. TaqMan analysis screened for YWHAH SNPs rs2246704, rs2853884, rs3747158, rs4820059, rs7291050, rs933226. Primary endpoint was presence of at least one copy of the YWHAH SNPs with the markers of RA disease severity.
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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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Photogram - Image Comparison and Identification

A human being is having physical and biological body structure, even though each and every individual is having his own blood group, hair color, retina color, skin complexes, height, breadth etc. that result in his own bodily structure that differentiates with the other individual. After the certain age of subject nearly about twenty years, height or length of his organs or limbs are not increases and fixed bodily structure is built up.
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Hyperkinetic Manifestation in a Patient with Hippocampal Atrophy

Describes a case of a patient that presents with hippocampal atrophy leading to hyperkinetic crises of parietal-occipital origin
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Self-reported Attributes of Police-chiefs Compared to Civil Leadership: Tolerance; Social Interest and Communication

This study has a focus on patterns of work-related interactions, experiences, and attitudes expressed by leaders in the Swedish Police force.A cross-sectional design was used to compare police leaders (n=106) with reference groups recruited for public and private enterprises (n=1650). Work-related ratings were provided by use of a recruitment inventory JobMatch Talent (JMT). In this study, three main JMT scales (including subscales) concerned with relationships were used: Tolerance (h1: Assent image, h2: Tolerant attitude, h3: Trust in others); Social Interest (i1: Showing consideration, i2: Diplomacy, i3: Contact creating); Communication (j1: Impact, j2: Communicative, j3: Openness).
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Self-reported Attributes of Police-chiefs Compared to Civil Leadership: Tolerance; Social Interest and Communication

This study has a focus on patterns of work-related interactions, experiences, and attitudes expressed by leaders in the Swedish Police force.A cross-sectional design was used to compare police leaders (n=106) with reference groups recruited for public and private enterprises (n=1650). Work-related ratings were provided by use of a recruitment inventory JobMatch Talent (JMT).
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Effect of Levonorgestrel-Releasing Intrauterine System on Sexual and Urinary Functions

The effects of the levonorgestrel-intrauterine system (LNG-IUS) on urinary and sexual functions of women with idiopathic menorrhagia were evaluated using two internationally validated questionnaire forms. This prospective study included (30-49) year-old women with idiopathic menorrhagia (n=91), who visited the Gynecology and Obstetrics Clinic of the hospital. The index of female sexual function (IFSF) questionnaire and the international consultation on incontinence modular questionnaire short form (ICIQ-UI) were used to evaluate sexual and urinary system functions, respectively, pre-, and 6 and 12 months post-LNG-IUS insertion. The IFSF scores were (mean ± SD) 27.1 ± 6.9, 30.0 ± 7.2, and 32.7 ± 7.5 at pre-, and 6 and 12 months post-LNG-IUS insertion, respectively (p<0.001). Compared with pre-LNG-IUS use among 91 patients, the IFSF score (symptoms improved) was increased in 47 and 60 patients and decreased (worsening symptoms) in 10 and 8 patients at 6 and 12 months post-LNG-IUS use, respectively. The ICIQ-UI scores were 4.9 ± 4.4, 3.7 ± 4.0, 2.8 ± 3.0 in pre-, 6, and 12 months post-LNG-IUS insertion, respectively (p<0.001). Compared with pre-LNG-IUS use, the ICIQ-UI score decreased (symptoms improved) in 33 women either in 6 or 12 months post-LNG-IUS use and increased (symptoms worsened) in 11 and 4 patients at 6 and 12 months post-LNG-IUS insertion, respectively.
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Treatment of Cerebral Mucormycosis with Prolonged Liposomal Amphotericin B (>1000 days)

Mucormycosis is a rare but invasive and potentially lethal infection caused by ubiquitous fungi of the order Mucorales. The primary mode of infection is inhalation of fungal spores. Rhinocerebral and pulmonary infections are most common, however, other organ systems including the central nervous system can be affected, presumably by occult fungemia. We describe the prolonged treatment course (>1000 days) of a patient with cerebral mucormycosis using liposomal amphotericin B (LAMB). Two different attempts were made to replace LAMB with posaconazole, but each occasion resulted in therapeutic failure. This case represents the longest course of LAMB reported in the literature.
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Research in Fracture Healing and Its Clinical Applications in the Veterinary Practice

Bone healing is a complex process consisting of multiple sequential phases needing the coordinated interaction of various cells, growth factors, cytokines and mechanical conditions. However, bone healing is one of the rare regenerative processes resulting in complete restoration of form and function. Fracture treatment aims towards a swift return to functional use of the injured limb. Therefore stabilization is a key requisite. In the veterinary clinic difficult fracture cases often require a unique stabilization by custom made external fixation. While this fixation technique harbors risk factors it offers a high flexibility essentially needed to successfully treat small animal fracture patients. Here we draw the connection between the up-to-date knowledge in bone healing and case reports of external fixation techniques from the small animal practice with respect to benefits and risk factors.
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Wildlife Forensic: Current Techniques and their limitations

The wildlife includes undomesticated and diverse forms of floral and faunal species, which is essential for ecological balance and human survival. The poaching and illegal trade has resulted in sharp decline of many wild species of flora and fauna around the world. The need of the time therefore is to utterly focus on wildlife protection for the sustainable development of biosphere and future viability of human beings. In this review we have focused on different techniques being utilized in wildlife forensic science for identification of wildlife species as well as their geographical origin. These techniques can be employed to control the wildlife crimes and convict the criminals involved in illegal trade of wildlife flora, fauna and their products. These techniques include footprints analyses, morphological and anatomical studies,
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Relationship between Weight Pre-Pregnancy and Weight Gain during Pregnancy with Preterm Birth

Worldwide alarming increase of obesity prevalence has led the WHO to take into consideration as one of the most serious global health problems of the 21st century. 40% of women worldwide are overweight. The leading causes of obesity prevalence in women more often becaouse during pregnancy and before pregnancy they gain excess weight. The rapid increase of obesity prevalence especially among women in the World cause women begin pregnancy overweight or obese and this can cause problems about pregnancy and birth.
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Production and Quality Evaluation of Instant Sorrel (Zobo) Drink Produced by Infusion, Dehydration and Size Reduction Methods

Instant sorrel drink (IZD) was developed by processing purple sorrel calyx into powdery form by the method of infusion, and dehydration and size reduction. Another purple sorrel calyx was processed into liquid zobo drink (LZD); and both the IZD and LZD were subjected to sensory evaluation using the total number of thirty five (35) panels of judges and data was subjected to t-test and preference test analytical tools; and found that IZD was also acceptable by the sensory panelists because the T-tabulated is 2.064, while T-calculated is -14.37 with standard deviations of 0.32 (P≥0.05) between the means; hence, there was no significance difference between the reconstituted IZD and the LZD, because T-calculated is not greater than the T-tabulated.
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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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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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Editorial Board Members Related to ions


Associate Professor
Department of Obstetrics and Gynecology
University of Arizona College of Medicine
United States

Henry Lawrence Dorkin

Associate Professor of Pediatrics
Harvard Medical School
Harvard University
United Stated

Alessia Giannetto

Department of Chemical, Biological, Pharmaceutical and Environmental Sciences
University of Messina

Martin Kroger

Department of Materials
ETH Zurich

Lihua Song

Associate Professor
Chief, Laboratory of Rickettsiology
Beijing Institute of Microbiology and Epidemiology


Associate Professor
Department of Medicine and Therapeutics
The Chinese University of Hong Kong
Hong Kong SAR


Toxicogenomics and Predictive Toxicology Division


Adjunct Professor
Pennington Biomedical Research Center
Louisiana State University
United States

Isik Yulug

Associate professor
Department of Molecular Biology and Genetics
Bilkent University


Associate Professor
Department of Pathology, Microbiology and Immunology
University of South Carolina
United States
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