Reseapro

Venous skin ulcers also known as stasis ulcers or varicose ulcers are chronic wounds caused by the poor blood circulation in the venous valves or veins, usually occurring in the lower part of the legs, between the ankle and the calf. This condition is known venous insufficiency and accounts for roughly 70 % to 90% of leg ulcer cases. These ulcers are often recurring, extremely painful and can take months and years to heal. This condition affects approximately 500,000 Americans annually, and the number is expected to increase as the rate of obesity climbs. It is estimated that the financial burden for the treatment of venous skin ulcers costs US healthcare systems over one billion dollars per year and the monthly treatment costs could be as high as $2,400 a month. Current treatments for venous skin ulcers are either conservative management, such as compression therapy or invasive and expensive surgical procedures, such as skin grafts. Other available treatment options include mechanical treatment and medications. The most standard treatment however involves the infection control, wound dressings and compression therapy in which patients are asked to wear elastic stockings to help improve leg circulation. Nevertheless, all these approaches were not found to be successful in every case and these wounds take often months or sometime years to heal.

Designing Ultrasound patch:

Recently, a team of researchers led by Dr. Peter A. Lewin at Drexel University at Philadelphia have designed a novel non-invasive technique called “Ultrasound Patch” for treating chronic ulcers and wounds. This technique uses patches with a novel ultrasound applicator that can be worn effortlessly like a band-aid. In this alternative therapy, battery-powered patch sends low-frequency and low-intensity ultrasound waves directly to the wound site. The therapeutic benefits of ultrasound for wound healing were established in previous studies, but most of studies were performed with much higher frequencies, around 1-3 megahertz (MHz). Dr. Lewin believed that decreasing the frequency to 20–100 kilohertz (kHz) might work better with a reduced exposure. According to him, one of the biggest challenges in designing this technology was to build a battery-powered patch since most ultrasound transducers require a bulky apparatus which need to be fixed on the wall. Dr. Lewin and colleagues also wanted to create something which is portable and can be easily worn for which the device has to be essentially battery operated. To accomplish this, they designed a transducer that could produce medically pertinent energy levels using minimum voltage. The ultrasound patch in its present form, weighs approximately 100 grams and required two rechargeable AA batteries. It is designed to be worn over the ulcer or the wound and the patient can deliver controlled pulses of ultrasound directly to the wound, while at home. The funding for this study was received from the National Institute of Biomedical Imaging and Bioengineering (NIBIB), a part of the National Institutes of Health.

Clinical studies for testing Ultrasound patch

To determine the optimal frequency and treatment duration of ultrasound patch, the study trial was carried out initially in total 20 patients, divided into four groups. Each group received either 20 kHz for 15 minutes, 20 kHz for 45 minutes 100 kHz for 15 minutes, or 15 minutes of a placebo or control which received no radiation.  According to the researchers, the first group was the one that eventually came out best, where all the five participants completely healed by the time they reached their fourth session. In contrast, the ulcers of the patients in the placebo group worsened over the similar duration. Results suggested that patients who received this low-frequency, low-intensity ultrasound therapy during their weekly follow ups (in addition to the standard compression therapy), showed a net reduction in wound size just after four weeks of the therapy. Whereas, the patients who did not received the ultrasound treatment had an average increase in the wound size. The team’s clinical findings were further confirmed by their in vitro studies where after 24 hours of receiving 20 kHz ultrasound for 15 minutes, mouse fibroblasts cells that play an active role in wound healing showed a 32% increase in cell metabolism and a 40% increase in cell proliferation as compared to the control cells. These findings are yet to be published in the Journal of the Acoustical Society of America.

Advantages and applications of Ultrasound patch

Antibiotic Resistance: Cause and Mechanism

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).

Antibiotics: Wonder drugs or a threat to public health?

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”.

Tips for Content Development

This article provides some basic tips on content development to follow while writing any content for blogs, websites, etc.

Pharmacogenomics: Its Origin, Applications and Challenges :

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.

Place names of several major cities, roads, flyovers, bridges, airports, and even small and insignificant chowks in nascent cities and towns have had a “makeover” in modern times. Most of these changes in place names have been effected almost as an afterthought and a sudden revitalization of regional pride.

The protagonists of the changes in place names would perhaps argue that this regional pride was always there, but a change in place names nearly always brings in controversy and therefore takes years to implement.  This might yet be true, and I have no qualms with regional pride as long as it does not impinge on the rights and interests of citizenry across the country. After all, culture in many parts of India is nurtured through a pride in the province and its heritage. Regional arts, crafts, and other expressions of originality in a state not only bind the region with a homogeneous cultural identity by which it receives recognition from other parts of the country, but also represent that state in the international arena. Delhi Chaat, vada pao and bhelpuri, appam, masala dosa, Bengali sweets, Karachi halwa, Banarasi paan, Kacchi dhabeli, and Hyderabadi biryani—the list is endless—are some culinary expressions of that regional pride, which is the identity of a particular city or region.

Place Names as Signage of History

Similar channels of identity can be found in textiles, dance, art, language, etc. Regional pride, therefore, might not be a bad thing at all, and changes in geographical names to preserve— or remind—the people about a particular region’s “originality” can thus be acceptable. But simultaneously, it might be argued that a place name is not just a dot and line on a map, but also a veritable identifier of settlements, civilizations, migrations, and reference points of history. Modernity has reduced these points of reference to relatively modern relevance only, feigning a cultural amnesia and shortening the life of the place, in a way.

The new place names that now find place on the map— undoubtedly after a bitter struggle to bring about the change—evoke nostalgia (the “regional pride”) of a few centuries at most. On the contrary, the names of yore go back manifold in time, recounting a history that is far more time elastic; millenniums, not just centuries, are associated with them. Naturally therefore, the “bias” of the historian—the writer included—generally lies with old nomenclature, simply because the old names conjure up imageries that paint a more complete picture of a particular place or region.

Change in a Place Name: The Psyche

It is not just in India that historical place names are being obliterated from the modern map. Starting from the 1820s, and through the 1990s, at least 38 countries and territories have shed their old place names for the new, and 66 cities globally are now known by their new names. India, too, seems to be afflicted by this trend; there are at least seven or eight major Indian cities that have seen a name change in modern times.

What, then, is the psyche behind this urge to change a toponym? The prime reason, as mentioned earlier, is to reinstate regional pride. In several cases, the changes were brought about by the end of colonial rule and establishment of a nationalistic fervor; in others, mergers or splits necessitated a change; in still others, cumbersome or unusual names were given up for more suitable or easier-sounding names. All these reasons are based on the fact that the “right” to a place name lies with the people who reside there, and their sentiments need to be respected.

Place names have changed, but “geographical souvenirs” of the discarded names still survive. Bombay is now Mumbai, but it is still the Bombay High Court, IIT Bombay, and Bombay Stock Exchange; Madras is now Chennai, but it is still University of Madras, Madras Stock Exchange, IIT Madras, and Madras High Court, Peking is now Beijing, but it is still Peking University; Pusan is now Busan, but it is still Pusan National University… Why? Obviously because established conventions die hard, regardless of the constant urge to move ahead and change the status quo.  And what does a name change hope to achieve? In the last decade of the 16th century, William Shakespeare expressed this sentiment:

“What’s in a name? That which we call a rose by any other name would smell as sweet.”

Romeo and Juliet (II, ii, 1-2), 16th century

And half a millennium later, we need to ask an almost identical question: Will a change in place name alter anything concrete in the people who live and react in a particular place? As former UN diplomat Shashi Tharoor writes:

This post describes about the passion, scope and limitations of a scientists in order to become a successful entrepreneurs.

After spending hours and days on your manuscript, won’t you spend a little more time to make it perfect? But, how would you know the correct way to improve your manuscript, or what amendments to make. Well, it’s not that simple, nor is it that difficult as well. The present post on “Tips To Improve Your Manuscript” provides seven essential tips that will enable you to know whether your manuscript is good or bad, and how to tell the difference. Simply follow these seven basic tips to improve your manuscript’s quality.

Seven Tips to Improve your Manuscript

 Print it out

Reading the manuscript on laptop and making amendments on it can be a bit hard and strenuous.

Instead, it is easier to detect errors on a printed page.

So, take a print out of the manuscript, relax yourself on the sofa, and start making corrections.

 Read it out loud

Read your manuscript out loud. This way, you can hear and easily detect any clumsy word, repetitions, extra long sentences and general errors in the text.

Try to write in a conversational manner.

Avoid being too formal. Thus, read out loud your copy and check what needs to be fixed.

 Spell-check

Spelling mistakes are one of the most common errors found in written manuscripts.

Check line by line to detect any spelling mistakes, misused words, and missing or incorrect apostrophes.

Be careful while checking grammatical errors and often-misused words, such as “they’re”, “their”, or “there”.

 Clarity

Carefully check the clarity and accuracy of text in your manuscript.

Can any sentence be shortened? Or could any sentence be made more clear?

Try to get your message across effectively. Use examples, if needed, to support your claims and clarify your point.

Avoid too many passive sentences. Instead, use action verbs wherever possible.

 Check these faults

Avoid anything awkward in your text. Because, if you find anything awkward, your reader will find it too. Ensure that your text runs smoothly.

Check for any confusing or unclear sentences. Ensure that your text is completely crisp and clear.

Provide adequate information for any facts that may seem otherwise unbelievable.

Avoid boring and dull sentences. Try to keep your text light and engaging, so that the reader can’t stop reading on.

 Use Track Changes

If you are editing or proofreading your manuscript using the MS Word, ensure to the Track Changes option.

This option allows you to track your editing and corrections, as well as accept or reject the changes made.

You can also use this option for keeping tabs on anyone else who is editing/proofreading your manuscript.

 Readability

Try to check the Flesch reading ease score of your manuscript. The finest copywriters try to maintain this around 80% or better. However, this is not always possible as in case of the manuscripts that has many technical terms.

Also, try to check the Flesch-Kincaid grade level score of your manuscript. Despite the age or intellect of your readers, try to keep your copy at the sixth grade level. Maintaining your manuscript in this level makes your text easier to read.

Interdisciplinary research – Direct Imaging of Single Molecule :

Modern scientific research does not confine itself to any restricted boundary.  Nowadays, it is all about interdisciplinary research. In 2012, Nobel Prize for Chemistry (http://www.nobelprize.org/nobel_prizes/chemistry/)was awarded to two eminent biologists, Prof. Robert J Lefkowitz and Prof. Brian Kobika, for their crucial contribution in unveiling the signalling mechanism of G protein-coupled receptors (GPCRs). It’s a lifetime work of both the scientists. Dr. Lefkowitz, an investigator at Howard Hughes Medical Institute (HHMI) at Duke University, is also James B Duke Professor of Medicine and of Biochemistry at Duke University Medical Center, Durham, NC, USA. Dr. Kobika, earlier a postdoctoral fellow in Dr. Lefkowitz’s laboratory, is currently Professor of Molecular and Cellular Physiology at Stanford University, School of Medicine, Stanford, CA, USA.

Transmembrane signalling of one GPCR “caught in action” by X-ray crystallography

GTP (guanosine triphosphate) binding proteins (G-protein) act as molecular switches in transmitting signals from different stimuli outside the cell to inside the cell. However, for doing this G-protein needs to be activated, and that is where GPCRs play the most important role. They sit in the cell membranes throughout the body. GPCRs, also known as seven transmembrane (pass through the cell membrane seven times) domain proteins, detect the external signals like odor, light, flavor as well as the signals within the body such as hormones, neurotransmitter.1 Once the GPCRs detect a signal, the signal is transduced in certain pathway and finally activate the G-protein. In response, the activated G-protein triggers different cellular processes. Binding of a signalling molecule or ligand to the GPCR causes conformational changes in the GPCR structure. As a result of extensive research of 20 long years, Dr. Lefkowitz and Dr. Kobika not only identified 800 members of GPCRs family in human but also caught in action how these receptor proteins actually carry out the signal transduction with the help of high resolution X-ray crystallography. The crystal structure of ß2-adrenergic receptor (ß2AR), a member of the human GPCRs family was reported by Dr. Kobika and his colleagues in 2007.2 The hormones adrenaline and noradrenaline are known to activate ß2AR, and the activated ß2AR triggers different biochemical processes which help in speeding up the heart and opening airways as body’s fight response. The ß2AR is a key ingredient in anti-asthma drugs. One of the major breakthroughs came in 2011 when Dr. Kobika and his co-workers unveiled for the first time the exact moment of the transmembrane signalling by a GPCR. They reported the crystal structure of “the active state ternary complex composed of agonist-occupied monomeric ß2AR and nucleotide-free Gs heterotrimer”.3 A major conformational change in ß2AR during signal transduction was discovered.

Now what is so special about GPCRs? Well, these proteins belong to one of the largest families of  all human proteins. GPCRs are involved in most of the physiological activities, and hence are  the targets of a number of drugs. Determination of the molecular structures of this class of receptors not only helps the researchers to understand the actual mechanism of different cellular processes but also help them to design life saving and more effective drugs. So, in a nut shell, this scientific breakthrough was possible due to the involvement of experts of different areas of science such as, chemistry, biochemistry, molecular and cellular biology, structural biology, cardiology, crystallography.

References

  Lefkowitz, R. J. Seven transmembrane receptors: something old, something new. Acta Physiol. (Oxf.) 190, 9–19 (2007).

Rasmussen, S. G. et al. Crystal structure of the human b2 adrenergic G-protein coupled receptor. Nature 450, 383–387 (2007).

Some people have unique talents, while some have interesting skills. Everyone is a master of something or the other. Where some are outstanding at sports, some are bright in studies. Similarly, some have a natural gift for writing, which when given proper guidance could be turned into a significant career. Content is undeniably sovereign while considering web-verse. Be it web-content, sales writing, SEO writing, magazine article writing, corporate-profile writing, press-release writing, e-books, etc. With so many varieties of areas depending on content writing, one should integrate the proper skills and techniques required for content writing. Besides, by following some specific guidelines for content writing, one can efficiently write a piece of content that not only attracts readers, but also ranks fine on the search engines.

Many of us have often come across the terms “peer review”, “peer-reviewed journal” or “peer-reviewed paper” at some or the other point of time. But, how many of us know what exactly the term “peer review” refers to or what the “peer review process” is all about? Let us discuss this key aspect of the research process.

According to the International Committee of Medical Journal Editors (ICMJE), peer review is the critical assessment of manuscripts submitted to journals by experts who are not part of the editorial staff. Peer review, which is also known as refereeing, has become an inevitable part of the quality control process, which determines whether a paper is worth publishing/funding or not.

Many of us have often come across the terms “peer review”, “peer-reviewed journal” or “peer-reviewed paper” at some or the other point of time. But, how many of us know what exactly the term “peer review” refers to or what the “peer review process” is all about? Let us discuss this key aspect of the research process.

According to the International Committee of Medical Journal Editors (ICMJE), peer review is the critical assessment of manuscripts submitted to journals by experts who are not part of the editorial staff. Peer review, which is also known as refereeing, has become an inevitable part of the quality control process, which determines whether a paper is worth publishing/funding or not.