Friday, September 10, 2010

Switching Completely to Linux Operating System

By Bishnu Marasini 
       Although my engrossment in electronics as well as better understanding of computer hardware, I have not been working significantly in this field for 10 years (used to do at initial days). Only, as amateur technical support for my colleague is being the use and sharing of my expertise. While, parallel use of both Windows OS and Linux OS more than 10 years, I, now realized to switch completely towards Linux OS because of the following reasons.
  1. To Get rid of Virus: Windows XP is too old to resist virus attack, Windows Vista and Windows 7 also susceptible to attack, the pirated version are even worse. Linux OS might not have pulled hackers’ intention to enervate which may be due to fewer users and free/Open Source Software.
  2. Hardware Compatibility: The latest version of Microsoft like Windows Vista and Windows 7 cannot be installed or are very slow on the older CPU and Motherboard. The latest Linux OS always takes care of older CPU and motherboards but depends on the distro (type) of Linux.
  3. Better Understanding of Programming Code and Software Pleothera: Linux is free and Open Source Software and can be modified by anyone and redistribute the OS and we can read and copy every codes associated with it. This feature has been helping me to understand the meaning of code and my experiments in modifying only few terms from the code file and to see the ultimate effects. However, I have not developed any application.
  4. Better Security of Files/Pictures/Folders etc. I have very bad experience of corruption of my word (*.doc), excel (*.xls), pdf, pictures (*.jpg) while keeping them under XP OS. Which were damaged and decoded if could be opened. Fortunately, I have not lost them (except few due to backup duration/period cycle) because of monthly backup of data in Linux OS.
  5. Easy and Quicker Initial Installation of OS: Linux OS have the feature of complete installation along with all basic drivers e.g., driver of monitor, motherboard, audio drive, printer etc. in a single initial install. All of these drivers would have to be installed after the main Windows OS which ultimately increase installation time.
  6. Live CD: Because of live CD it made easier to understand, view features without any change and installation in hard disk. This also helps to restore/copy files and folder accidently deleted even in case of OS failure/crash.
  7. Swiftness: I have noticed that opening any application and internet search is very fast in Linux compared to Windows OS. Need for installation of anti-virus software and virus attack might impede the performance of Windows OS.
       Linux is free and becoming user friendly, but still more than 85% people pay to Microsoft/Apple Inc. for the same service because Linux OS still has many limitation.
  1. Difficult for Beginner of PC Users: Windows OS is easily understandable and could be one mouse click operation. Also, institute/schools use Windows OS to train basic computer, so they feel easy to use it in future days. However, some distros like Fedora, Ubuntu, OpenSuse, etc. have been progressing a lot in graphical user interface (GUI) so that it would be like Windows OS. They have improved in GNOME, KDE, Xfce, etc. desktop environment.
  2. Some Software and Games are not for Linux: Most of the daily required Software like MSOffice, ChemDraw, NamePro, SoftMax, ACD, Adobe Photoshop, Dreamweaver, etc. are only for Windows and can’t be installed in Linux. An adapter-like (emulator) software known as “Wine” facilitates to install these software in the Linux OS. But Wine has not exhibited satisfactory result in complete installation of most of the above applications. Also, it (Wine) opens the gate and vulnerability of virus to Linux root.
  3. Connection of Instruments to PC: Most instruments such as ELISA Reader, Microscope, PCR, etc., and even some printer can’t be connected to PC of Linux OS or if connected,  their full capacity enervated. A Distro “Scientific Linux” derived from Fedora and RHEL, "Scibuntu (UbuntuScience)" derived from Ubuntu may become better OS in future days not only to support such kind of scientific equipments but also better view of molecule’s, Protein’s, and DNA’s 3D structures in Linux OS.
  4. System Crash: As this OS is free and supported and built by community; some of its application and whole OS vulnerable to crash and should be debugged. The Distro “Debian” is found to be most stable but it is usually found to be outdated in comparison to other Linux Distro.
       At last, our smaller and smaller contribution like reporting of bug found in crash e.g., my report (, sharing of scientific knowledge helps the volunteer engineer/developer to make Linux as better OS in future days. Also, we’ll not be accused of using pirated software used as lured by easiness and better performance; without paying in these days.
       I am currently using Fedora 12/13 as it is updated in every six months and latest repository and application of Linux is available via Fedora than other distro.

Wednesday, September 01, 2010

Identification of Beta-lactamase Inhibitor; a Strategy for Drug Development against Antibiotics Resistant Bacteria

Introduction:                                                                             By Bishnu Marasini

       The most threatening to human health is due to bacterial infection and intensive research has been addressing to treat these maladies since the known history. The infectious bacteria are microscopic, unicellular prokaryotes and different than mammalian eukaryotic cells. The outer layer of the bacterial cell consists of cell wall which is not found in mammalian cell and can be taken as target for development of bactericidal agents. The finding of clear zone of inhibition of bacterial culture around the growth of Penicillium notatum in the experiment of Alexander Fleming in 1928 was the positive indication to get rid of such threat.
       Nowadays almost all bacterial infection can be cured using antibiotics. The world consumes tons of antibiotics per year and half of them are beta-lactam type e.g. penicillin, amoxicillin, cephalosporin, cephalexin, cefixime, ceftriaxome, monobactam, carbapenem, methicillin etc. Beta-lactam antibiotics have broad spectrum activity, economical friendly on production, good safety profile, have clinical efficacy. It is also target specific for prokaryotic cells, little side effects except some allergic reaction. So, it has gained wide popularity.
       One of the components of bacterial cell wall is peptidoglycan which is cross linked polymer of repeatedly units of N-acetylglucosamine (NAG) and N-acetylmuramic acid (NAM). The final step in cell wall biosynthesis is transamidation reaction catalyzed by the enzyme cell wall transamidase (CWT) also called as penicillin binding protein (PBP). This enzyme helps to cross link the polymer of NAG and NAM. The highly strained and reactive beta-lactam ring of the antibiotics reacts and binds irreversibly with the serine hydroxyl group of PBP (shown in figure 1) which inactivates the enzyme and ultimately death of bacteria (Frère et al, 1984; Tipper and Strominger, 1965).

Figure1: Binding of β-lactam Ring with Penicillin Binding Protein
       However, beta-lactam antibiotics are becoming ineffective against pathogenic bacteria. The most common reason is due to the production of beta-lactamase enzyme (EC which catalyze the hydrolysis of the antibiotics i.e., formation of carboxyl group degrading beta-lactam ring (Shown in figure 2). Hydrolyzed antibiotics lose its activity or binding affinity towards the PBP hence no effect against bacteria. Hydrolysis of beta-lactam is rapid by beta-lactamase than binding of beta-lactam to PBP (Bush 1988)

Figure 2: Degradation of β-lactam ring by β-lactamase enzyme
       The beta-lactamse (penicillinase) was reported just few years after the first antibiotic discovered (Abraham and Chain, 1940). Although penicillin is the oldest antibiotic and most of the organisms acquired resistant, it is first therapeutic choice in some diseases like syphilis. Beta-lactamse enzyme is an extra cellular enzyme in Gram-positive bacteria and found in periplasmic membrane in Gram-negative bacteria (Bowden and Georgiou, 1990; Dyke and Richmond, 1967). More than 200 types of beta-lactamse have been found (Bush et al, 1995). The difference among them is only the catalytic efficacy and turn over rate range from 0.004 to 1,200 molecules per second by 1 molecule of enzyme. Among them two types i.e. penicillinase and cephalosporinase type has a potent influence on the profile of the beta-lactam resistant antibiotics. Class A beta-lactamse has high affinity towards penicillin G but low affinity towards cephalosporin while class C beta-lactamse has opposite. Class B beta-lactamse hydrolyze the antibiotics by binding with the co-factor zinc (Zn) and class A, C and D hydrolyze by binding through serine residue of it to beta-lactam ring (Sawai et al, 1981). Beta-lactamase became widespread via the mechanism of plasmid exchange/insert among the pathogens (Sykes and Richmond, 1970). The rapid spread and evolution of these enzymes have seriously threatened the present antimicrobial arsenal.
       Two strategies have been developed to combat the problem of resistant. The first approach has been the synthesis/production of beta-lactamase resistant antibiotics e.g. penicillinase resistant beta-lactam antibiotics, nafcillin, oxacillin, ceftriaxone, cefoxitime, aztreonam, imipenem etc. But after few exposure to pathogens these antibiotics also become susceptible to extended spectrum beta-lactamase (ESBL) produced by multi-drug resistant (MDR) pathogens.
       The second approach is to use beta-lactamase inhibitors coupled with beta-lactam antibiotics. These enzyme inhibitors function to permanently inactivate the beta-lactamase in the periplasmic space so that the partner antibiotics can reach its target, penicillin binding protein (PBP). Broad spectrum beta-lactam antibiotics plus beta-lactamase inhibitors combination have been found good safety records and clinical efficacies (Munoz et al, 1996). Augmentin, the production of GlaxoSmithKline which is composed of amoxicillin and clavulanate in 2:1; Timentin (ticarcillin and clavulanate); Sultamicillin (ampicillin and sulbactam) are examples of beta-lactamase inhibitors in combination with beta-lactam used clinically. Clavulanate exhibited clinical efficacy than others and used as standard inhibitor. However, clavulanate was not found so effective against class C beta-lactamase (cephalorinase type) (Bush K, 1989). It also exhibited side effects on the long term of use like liver function destruction, gastrointestinal toxicity etc. (Ioannidis et al, 2002). Also it contains beta-lactam ring it and may be susceptible to beta-lactamase enzyme in upcoming days as broad spectrum beta-lactam antibiotics which were resistant to beta-lactamase, now become susceptible.