A research team at Imperial College London and the Medical Research Council has finally been able to use Artificial intelligence to forecast outcomes for heart patients, aiding doctors to find the best treatment for individual patients. The technology outperformed doctors, being able to correctly predict a patient’s diagnosis 75% of the time. It is hoped that the new technology will assist doctors to spot clinically useful information from heart scans that would be missed by a human eye enabling them to take an action at the earlier stage.
A noteworthy fraction of the topmost doctors fail to reveal their financial relationship with the drug companies in the guidelines. A massive research investigation in the United States found a link between marketing payments to doctors and local deaths from opioids. It was found that only one-third of the guideline writers had a potential relevant tie to a drug company and the rest was not disclosed. This is a huge matter of concern as the guidelines put big impacts on the sort of care a patient receives from doctor, and on which drugs they prescribe.
After continuous protests claiming modification of stipends for research scholars, the government finally announced a hike in the monthly payments of the research fellows. Junior research fellows will now get Rs 31,000 p.m. and Senior research fellows will get 35,000 p.m., a hike of roughly 20%. Stipends for Research Assistants would now range from Rs 47,000 to Rs 54,000 p.m. This is the lowest increase in stipends since 2010. The research scholars are apparently disappointed with the sanctioned hike and have said that they would continue their ongoing protest against the insignificant increase in stipends.
Only a few technologies in the world are hotter than Artificial Intelligence in recent times. It has been the cause of the technological breakthroughs in past several years-from robots to Tesla(TSLA). With the advancement of the same and several agencies and firms taking huge interest in Artificial intelligence, it is expected to watch out for self-driving cars ; self-automated health care equipment’s; robots that can actually make coffee, watch TV or something along these lines , and much more in the very future. Sanja Fidler, assistant professor of computer science at university of Toronto says, ”Toronto is going to be the next Silicon Valley”.
Writers often struggle with their writings because of a loss in concentration or a paucity of ideas. They seem to have come to a dead end with no idea what to write. It is as if they have hit a block in their thought processes–a writer’s block–with no clear indication what to include in their writings or how to continue writing.
Almost every writer faces this writer’s block at some point in their writing careers, and most of them have come out of it with a stronger intent to complete their writings. Here are some simple tricks that can help you overcome writer’s block.
Minimize distractions. Unnecessary distractions can cause writers to lose their focus and get stuck in the middle of their writing. For this, you need to minimize such distractions as much as possible. Some tricks to minimize distractions include switching off mobiles phones, disconnecting from the Internet if not required, creating daily routines for writing, and working in solitude if possible. These tricks can help you improve concentration and generate new ideas for your writing.
Focus on other things. Sometimes, focusing on things other than writing can help clear the blockage and spawn new ideas. You need to divert the mind away from writing so as to refresh it. You can opt to do something creative such as painting or cooking, or simply laze around by listening to music or reading books. Performing mild exercises also helps clear the mind. Walking or playing outdoor or indoor games can give you a fresh and new perspective on your writing.
Change your writing environment. Check whether your working environment is comfortable. Consider writing in another environment, such as a coffee shop, for a change. A change in the workspace can help you generate fresh and new ideas for your writing. You can also create or remodel your own workspace by adjusting few factors like changing the lighting or using brighter lights at the desk. You may also try changing your desk and chair or your room. Whatever trick you use, the basic point is that a new environment will help you clear your blockage and increase your focus on writing.
Spend time with loved ones. If you are stuck with your writing, the best thing you can do is spend time with someone who makes you feel good. You may call an old friend or hang out with your friends. You can also spend time with your family or go out for a walk with your dog. Whatever you do, spending time with your loved ones will definitely make you happy and help clear your blockage.
Do free-writing. Have you ever considered writing down your random thoughts? Spend 15–20 minutes writing freely on any topic you like. You can write on your frustrations or your views on current affairs. You can change the subjects, but make sure you write randomly without any care for punctuations. These free-writing entries can inspire you with new ideas for your writings and will also clear your blockage. You can jot down the ideas in bullet points for easy accessibility when needed.
Read some inspiring quotes before writing. Before beginning your writing assignment, try reading some inspiring quotes. Inspirational quotes can motivate you and help you develop fresh and new ideas to use in your writings. In addition, inspirational quotes can also help you with new topics or stories for your writings.
Set deadlines and keep them. Many writers find it difficult to set a deadline for themselves and complete their writing projects within the set deadline. To circumvent this problem, you might find a writing partner and agree to hold each other to deadlines in an encouraging, uncritical way. Writing groups or classes are also good options to jump-start a writing routine.
Take a break after completing a project. Writer’s block could be an indication that your ideas need time to develop. Idleness can be a key part of the creative process. After finishing a project, have some “me” time. Take a break between two projects so as to gather your thoughts and gain new experiences and ideas. You can spend time with your loved ones, or indulge in reading or other art forms before you start again.
A writer’s block is a temporary setback faced by most writers, regardless of how prolific they are in their creative output. At that point in time, it might seem to be too big a mountain to climb, but it is something that can be easily overcome. You must have self-belief to keep the creative flow going, and these tricks will go a long way in helping you achieve that.
Pyoderma gangrenosum (PG) is an immune-mediated, rare ulcerative disease of the skin. In general it occurs in a genetically susceptible individual. Its incidence ranges from 0.3-1.0/100,000 population. Female are affected more than males.
The cause of PG is not clear but it is attributed that the aberrant chemotaxis of neutrophil to the site of trauma causes development of primary lesion.
The primary lesions are usually small tender papule, pustule, folliculitis or nodule, which breakdown rapidly and progress to a large painful ulcer. The PG ulcer is characterized by violaceous undermined edges, and necrotic floor covered with purulent exudate and associated disproportionate pain. Rarely it may be non-tender. The ulcers last for months to years. The PG has the fluctuating course and it may deveop pathergy and lead to rapid enlargement of the disease.
There is no definite investigations to diagnose PG. To date, diagnosis of PG is by exclusion of other causes of ulcers, associated systemic diseases, correlation of histology with clinical feature or rapid response to high dose corticosteroid.
Treatment with Corticosteroid is satisfactory; cytotoxic drugs are rarely added for treatment of PG. The lesions usually heal with cribriform scar. Recurrence of this disease may occur.
The patient with diagnosis of PG are advised to avoid surgical procedure for the fear of recurrence through pathergy, but when surgery is required, the surgery should be carried out under the supersvion of Dermatologist for atleast 2-3 weeks after surgery to prevent pathergy.
Fluorescence spectroscopy has been applied to numerous analytical, bio-analytical, environmental, clinical and forensic investigations. There is a need for a highly sensitive detection tool that can replace the expensive and difficult to handle radioactive tracers, but at the same time the tool/method has to be of low cost, easy to handle and can detect analytes in rapid time. Fluorescence spectroscopy has answer to all these. To explain the highly sensitive detection capacity of fluorescence as a tool, Professor J.R. Lakowicz discussed an example in his book “The Principles of Fluorescence Spectroscopy”. He mentioned that since fluorescence intensity is measured directly in relatively dark background (see the inset figure) without the presence of bright reference beam as in case of absorbance, it becomes easy to measure even in low level of light, and electronic impulses of the single photon can be read by the most photomultiplier tubes.1 On the other hand, if we try to measure the absorbance of a solution of concentration 1 nanomolar (10-10 M) with molar extinction coefficient (e) of 10-5 M-1 cm-1, the absorbance will 10-5 per cm (%transmission= 99.9977). It is very difficult to measure only 0.0023% absorbed light even with highly sophisticated optical system. Following two schematic diagrams represent very basic model of UV-vis and fluorescence spectrophotometer which will help us to understand the technical difference between these two techniques regarding the sensitivity in measurement as explained above. This explains the high sensitivity of fluorescence spectroscopy as a detection tool.
Fluorescence based sensing technologies have been constantly growing with the invention of innovative methods and materials. I will discuss various applications based on fluorescence detection/sensing. Before that, we need to understand the different characteristics of fluorescence emission such as Stokes shift, fluorescence lifetime and quantum yield, steady and time-resolved fluorescence, fluorescence anisotropy, fluorescence quenching, fluorescence resonance energy transfer (FRET), and the molecular information obtained from these.
Fluorescence emission spectrum and Stokes shift
Stokes shift is the difference between the position of absorption band maximum and emission maximum of the same electronic transition in frequency or in wavelength unit (inset figure below). Fluorescence always occurs at the higher wavelength than the absorption. The reason can be attributed to the relaxation of the excited electron from the higher vibration energy level to lower vibrational level of S1 and further decay to higher vibrational energy level to S0. Thus, the excitation energy is lost by the thermalization of excess vibrational energy. Irish Physicist, Sir G. G. Stokes first reported this phenomenon in 1852. In addition to this, further Stokes shift can be observed due to solvent effect, pH, excited state reaction, complex formation and energy transfer. From the measurement of Stokes shift, different molecular information can be obtained. As fluorophores are generally sensitive to the environment, by examining the position and intensity of the emission spectrum location of moleculer probe (here the fluorophore attached to some macromolecules) inside a macromolecule can be identified. The property of certain fluorophore being weakly fluorescent in aqueous environment but strongly while binding to target biomolecule accompanied by Stokes shift has been widely used. Moreover, utilizing the environment sensitivity of certain flurophores for example indole group of tryptophan residue in protein may reveal whether the protein is in folded or unfolded (denatured) state. Emission from a residue shifts to longer wavelength once it is exposed to the surrounding solvent (here water) due to unfolding. In the folded state, the protein shields it from the solvent. Therefore, conformation of proteins can be obtained from emission intensity and Stokes shift (see the inset figure at the left).
I will talk about the other characteristics along with applications in the future posts. Continued……………
In this part, I will discuss some basic theories behind Fluorescence spectroscopy. In order to realize the potential of this particular spectroscopic technique, one must aware of the principle based on which this technique works. This will allow one to take complete advantage of this sensitive technique in applying in various scientific research.
Spectroscopy, in general, is applied quantum mechanics. Without going deep into the mathematical part, I will try to explain the basic principle of fluorescence spectroscopy rather qualitatively using Jablonski diagram.
Basic Principle of Fluorescence Spectroscopy:
Professor Jablonski, known as the father of fluorescence spectroscopy presented us with a diagram which describes various molecular processes in the excited state. As mentioned in my last blog that fluorophores play the central role in fluorescence. Prior to excitation with light (or photon), the electronic configuration of the fluorophore molecule is described as ground state. Upon absorbing photon the electrons of the fluorophore molecule get raised to higher energy electronic level. The phenomenon of fluorescence occurs when the excited electron comes back to the ground state from the higher electronic energy level by emitting photon. A typical Jablonski diagram is basically an energy level diagram which illustrates electronic states of a molecule and transitions between them. The electronic states are arranged vertically by energy and grouped horizontally by spin multiplicity (see the inset diagram). Radiative transition is depicted by solid arrows, while the nonradiative transition is shown by squiggly arrows. Within each electronic state there are multiple vibrational energy levels (electronic levels are depicted with thicker lines and the vibrational levels are with thinner lines). As shown in the inset figure, the singlet ground, first and second electronic excited states are depicted by S0, S1 and S2, respectively, while first and second triplet excited states are depicted by T1 and T2, respectively. In singlet state, all the electrons of a molecule have their spin paired, while in triplet state, one set of electron spin becomes unpaired. These two states differ in properties as well as in energies; the triplet states always lie in lower energy than its corresponding singlet state. The transition between singlet to triplet state is forbidden. The probability of singlet-triplet process is 10-6 of the singlet-singlet and triplet-triplet processes.
The first transition in the Jablonski diagram is ABSORPTION. When a fluorophore molecule (or any molecule of interest) absorbs photon of definite energy the electrons in the ground state (S0) is excited to a higher energy level (S1 or S2) depending on the amount of energy absorbed. The process is very fast, and the time scale of absorption is in the order of 10-15 seconds. Once the electron is excited, there are multiple processes by which it dissipates energy and return to the ground state. First through VIBRATIONAL RELAXATION (VR), a non-radiative by which the electron gives away the energy in vibrational mode in the form of kinetic energy, and returns to lowest vibrational level of the corresponding excited electronic state. The time scale of VR is in the order of 10-14-10-11 seconds. Another process of energy dissipation occurs via INTERNAL CONVERSION (IC). IC is mechanistically similar to VR, and it occurs when vibrational level strongly overlaps with the electronic level, the electron in the vibration level of higher excited electronic state may relax to the vibrational level of the lower excited electronic state. However, due to lack of overlap between the vibrational and electronic levels and a large energy difference between ground state and the first excited electronic state, the probability of an electron to return to ground state via IC is very less. FLUORESCENCE (Fl) is another path through which an electron can dissipate energy and return to ground state. The time scale of fluorescence is in the order of 10-9-10-7 seconds. From the lifetime, one can tell that IC is generally complete before emission. Fluorescence emission generally results from thermally equilibrated lowest energy vibration level of S1 to the highest energy vibration level of ground state (S0), which then quickly thermally equilibrated (VR), and returns to the lowest energy vibration level of ground state. This singlet-singlet transition is allowed. Since emission involves the transition to highest energy vibrational level of ground state, the emission spectrum is typically a mirror image of absorption spectrum of the S0 → S1 transition. Electronic transition does not alter much the nuclear configuration, so the spacing between the vibrational energy level of the excited state remains almost the same as in ground state. This is the reason behind the similar vibrational structure of absorption and emission spectrum of a fluorophore molecule. However, there exists many exception of this mirror image rule. In case of proton dissociation, excited state reactions, charge-transfer complex formation, dimerization, one can observe deviation from the mirror symmetry rule.
Another process of non-radiative energy dissipation is known as INTER SYSTEM CROSSING (ISC) which involves a forbidden transition, where the electron changes spin multiplicity from excited singlet state (S1) to excited triplet state (T1). The emission from T1 to singlet ground state (S0) is known as PHOSPHORESCENCE and this forbidden transition is associated with several order smaller rate constant than that of fluorescence. The lifetime of phosphorescence is quite longer, in the order of 10-4 second to 1 minute.
1. Jihad René Albani. Principles and Applications of Fluorescence Spectroscopy. Blackwell Science Ltd, 9600 Garsington Road, Oxford OX4 2DQ, UK. Edition 2007.
2. Joseph R. Lakowicz. Principles of Fluorescence Spectroscopy.Third Edition. Springer.
Fluorescence spectroscopy, a very sensitive analytical tool, has wide ranges of application in various disciplines of scientific/medical research. I am going to write a series of blog-posts discussing its numerous applications. To begin with, let me first go back to the history; how “FLUORESCENCE” was discovered, and evolved as a primary research tool in diverse fields of scientific research such as chemistry, biochemistry, biophysics, biotechnology, genetics, forensic, medical diagnostics, etc. to name a few.
A Short History of Fluorescence:
Nicholás Monardes, a Spanish physician and botanist observed a bluish opalescence from water infusion of a wood of a small Mexican tree. In 1565, he described about this observation in the Historia medicinal de lascosasque se traen de nuestras Indias Occidentales. A Franciscan missionary named Bernardino de Sahagún also independently observed similar observation for the wood named “coatli”, around same time. He reported in the Florentine Codex, “Coatli …..patli, yoanaqujxtiloni, matlaticiniayoaxixpatli..“, which means “it is a medicine, and makes the water of blue color, its juice is medicinal for the urine”. In 1574, Charles de L’Écluse, a Flemish botanist named Monardes’s wood as Lignum Nephriticum (kidney wood) because of its therapeutic properties in treating kidney related ailments. Thereafter, many scientists reported this type of luminescence property in various substances such as chlorophyll, barium sulfate, etc. Sir John Frederich William Herchel first observed the fluorescence from a solution of quinine sulfate (in tartaric acid) in sunlight in 1845, and described it as “beautiful celestial blue color”. This was published in Philosophical Translation of the Royal Society of London (1845) 135:143–145. Sir John Herchel termed this phenomenon as “epipolic dispersion”. [Inset figure shows the fluorescence from a quinine sulfate solution.] Later in 1852, G.G. Stokes published a very long article (more than 100 pages), “On the change of Refrangibility of Light”, where he mentioned about his disagreement on Sir John Herchel’s term of “epipolic dispersion”, and wrote; “I confess I do not like this term. I am almost inclined to coin a word, and call the appearance fluorescence from fluor-spar, as the analogous term opalescence is derived from a mineral.” G.G. Stokes was the first person who proposed to use fluorescence as an analytical tool in a lecture “On the application of the optical properties to detection and discrimination of organic substances” in 1864. Following are the important research works done in much earlier days (1904-1942), which immensely contributed to the understanding, improvement and advancement in Fluorescence spectroscopy as a technology.
1905: The first excitation spectrum of a dye – E. Nichols and E. Merrit
1919: Fluorescence quenching – Stern and Volmer
1924: Determination of fluorescence yield -S.J. Vavilov
1925: Theory of fluorescence polarization-F. Perrin
1926: First direct measurement of nanosecond lifetime – E. Gaviola
1935: Jablonskidiagram – A. Jablonski
1948: QM theory of dipole-dipole interaction – T. Förster
Fluorophores are mainly organic compounds which play the central role in fluorescence. They not only absorb light of specific wavelength, but also emit light at specific wavelength. The energy of this emitted light depends on the fluorophore as well as on the surrounding environment of the fluorophore. R.Meyer in 1897 first coined the term “fluorophores” to describe those compounds or the specific functional groups responsible for the phenomenon of fluorescence. A lot of fluorophores has been discovered such as fluorosceine, eosine, quinine, rhodamine, acridine, etc. to name a few. The first fluorometric analysis was performed by F. Goppelsröderin 1867 for the quantitative determination of Al(III) from the fluorescence of its morin chelate. Otto Heimstaedt and Heinrich Lehmann (1911-1913) first developed the fluorescence microscope to investigate the autofluoresecence of biosamples such as bacteria, protozoa, plant, and animal tissues. Later, American Instrument Company (AMINCO) collaborated with Dr. Robert Bowman who designed the instrument and marketed first ever spectrophotofluorimeter (SPF) in 1956 (inset picture) (http://history.nih.gov/exhibits/bowman/HSfluor.htm). Antimalarial research actually initiated the invention of a spectrophotofluorimeter as an analytical instrument which can determine the presence of analytes which fluoresce. The story dated back to 1940, during World War II, when scientists in USA required to determine the amount of drug reached to the malaria parasites in patient’s blood for a clinical trial of antimalarial drugs. Bernard Brodie and Sidney Udenfriend of Goldwater Memorial Hospital in New York City designed a new test using an instrument called fluorimeter which can determine the amount of the drugs in the blood plasma from the intensity of the fluorescence emitting from the drug, since many of the drugs used in the trial fluoresce. This helped them to come up with a critical dose of a drug minimizing the adverse side effects. Atabrine was one such promising drug which destroys malaria parasite effectively. Scientists at Goldwater realized that this technique has immense potential in scientific research, and needed a better instrument to utilize the full potential of this new spectroscopic technique. Dr. James Shannon, the leader of antimalarial research at Goldwater became the first director of NIH (National Institute of Health) at Bethesda, Maryland, USA, and recruited a team of scientists to design a new instrument utilizing the principles of fluorescence. Dr. Robert Bowman led this team and came up with the design of first spectrophotofluorimeter. Invention of spectrophotofluorimeter was indeed an exciting journey which started with a need to destroy the malaria parasite effectively. This is another example of the famous English proverb “Necessity is the Mother of Invention”.
Come back to know more about fluorescence. In a series of posts, I will explain basic principles of fluorescence spectroscopy and its various applications in a qualitative manner, which may help beginners to understand the potential of this particular spectroscopy in scientific research.
One may certainly ask what is so exceptional about writing a dissertation or why is a dissertation given so much importance. Well, the answer is simple enough. As long as you are an academic student, things usually do not come your way as tough as they would once you begin your final academic years as a student going into a professional field.
The present article on “Writing a Dissertation” will effectively guide you through the journey about what is a dissertation and how to prepare a dissertation.
Tips for Writing a Dissertation
A new process
In school or college, we have usually written essays and compositions that are not completely our own writing, but borrowed from some essay books, expansions to our textbooks, or references provided by our teachers, etc. However, writing a dissertation is totally different from writing an essay. Dissertation writing is an entirely new process that is exceptional in every way. It releases the prospects of our academic knowledge and puts together all our research papers giving us a completely new viewpoint from thinking as a student to a professional.
A genuine work
Writing a dissertation is an individual’s work. You are an independent person, who is free to select any appropriate topic, work day and night, design the dissertation, edit and re-edit it, etc. You have to do your own research and get your findings. Prepare your dissertation in such a way that it not only looks perfect, but stands supreme amongst the rest and conveys genuineness to your work.
A process of growth
Gone are the days when your teachers and advisors where there to help you. While writing a dissertation, you would be on your own and thus it is obvious to begin thinking like a professional. In fact, your career transforms quite substantially. The significance of writing a dissertation has its immense value as it enables you to focus your future in trying to render the best of your present.
Improves your skills
Dissertation writing not only polishes your writing skills, but also improves your analytical skills. Moreover, it expands your world outlook and increases your literary skills. Eventually, you might feel confident about starting to write independently, or arise with an idea to start your own routine dissertation writing service where students can avail online dissertation assistance from you.
Boost for your career
A thoroughly written and prepared dissertation, which covers all chief components necessary for making an impressive document, could prove to be quite valuable in giving your career a boost. It has been noticed that many fellow students have, in fact, found jobs on the basis of their dissertation. Thus, it is possible that a very well done dissertation could be your access to a successful career.
Don’t get overworked
Dissertation writing needs a lot of brain work, so it can be much stressful and tiring. Therefore, it is necessary not to overwork or stress ourselves. If is required to maintain a balance or a time table and let the work be smooth and trouble-free.
Take help from professionals
Writing a dissertation needs great effort. You may sometimes find yourself stuck at some point, or be unable to understand how to begin or from where to start. In such situations, it is beneficial to seek the help of dissertation writing experts who are experienced enough to assist you with your dissertation. You can also take guidance from professional writers who can professionally help you during each and every step of your dissertation writing.
In order to achieve the degree that can enable one to make an independent choice to excel in any profession, one has to put his/her intellectual instincts, knowledge and experiences into a dissertation. Hence, writing a dissertation is not only essential, but is also compulsory for students. By adhering to the above mentioned tips, you will not only understand the concept of dissertation writing, but also how to prepare it.