Guide for all the Researchers
Research Ideas i.e. What to know? (Actual Phrases)
Biology:
Biochemistry
Genetics
Biotechnology
Biotechnology
2004:
More complex gene regulatory modules and interfaces need to be constructed to fully realize the capabilities of modular genetic control circuits. This could enable sophisticated processing capabilities, including event counting and signal integration. (Kobayashi, et al., 2004)
2009:
An entire molecular species is either in state Off (i.e. low concentration) or On (i.e. high concentration). An inherent difficulty with both interpreting and engineering digital reaction networks lies in the arbitrary definition of Off and On states. Clearly, concentrations can take any value between zero and infinity, and while defining the Off state is easy, doing so for the On state has to be justified. (Benenson, 2009) (On and Off represents to work or not to work respectively)
Predicting gene regulatory function from first principles still remains a major challenge. Moreover, even if such tools existed, they would not be able to tell us how to connect arbitrary transcription factor inputs to a specified output gene in a desired fashion – something we would expect from a programmable system. Engineering specified regulatory behaviors with arbitrary transcriptional regulators is therefore one of the main unsolved issues in synthetic biology and molecular computing. (Benenson, 2009)
It is somewhat surprising that despite solid theoretical foundations and intellectual maturity, actual implementation of large-scale transcriptional logic networks has been limited. Granted, many exciting synthetic networks with interesting properties relied solely on cascades of inverters or activators, or included negative and positive feedbacks. (Benenson, 2009)
There are also generic challenges pertaining to putting together and testing tens of gene components in a biological context. (Benenson, 2009)
There are intrinsic time delays for propagating the signal through multiple layers, as each stage requires both transcription and translation of protein92. Characteristic times required to accomplish this task depend on the host organisms, and non-surprisingly they are connected to other time scales of the hosts, in particular generation time. In applications where time is an issue, using more than three-four layers will make the network compute longer than it takes for the host cell to divide, leading to loss of resolution. Signal dissipation due to biological “noise”in deep cascades is another issue to consider. It is also interesting to note that nature's own transcriptional “computations” are rarely deeper than 2-3 layers, reflecting similar constraints. An alternative to deep cascades are wide and shallow circuits. Logic “normal forms” naturally lend themselves to such circuit architecture, but theoretical proposals to build such circuits79 have not been implemented yet. All the above challenges, however difficult, are well worth solving because transcription factors can be coupled to a large number of input peripherals. (Benenson, 2009)
In parallel, numerous technical issues will have to be solved, for example low-cost, rapid assembly of 20+ component circuits. Currently-available gene synthesis technologies are still costly and time-consuming. Another question pertains to the development of “debugging” tools, in other words, how will we know if such a complex network operates properly under all possible conditions? Yet another challenge is implanting these circuits in live cells, be it bacteria, yeast or mammalian cells. Each organism is different and each will attempt to bypass the newly introduced network. (Benenson, 2009)
Pharmaceutics:
2006: “The processes involved in delivery of these carriers (liposomes) and release of active agent, the variability of such processes (preferential accumulation of liposomes in the tumor area), and the degree to which the active agent is released into the tumor’s extracellular fluid or into tumor cells, are still unknown.” (Immordino, Dosio, & Cattel, 2006)
“Unfortunately, the effect of GM1 liposomes in prolonging half-life in bloodstream has been observed only in mouse models.” (Immordino, Dosio, & Cattel, 2006)
“A conclusive link has not yet been established between chemical and physical properties of PEG (polyethylene Glycol) and its ability to extend circulation lifetime. Although the accepted opinion is that PEG increases circulation longevity of drug carriers by reducing or preventing protein binding and/or by inhibiting cell binding/uptake, there is sufficient conflicting data to warrant a reassessment of the mechanism(s) by which surface grafted PEGs improve liposome properties.” (Immordino, Dosio, & Cattel, 2006)
“Stealth liposomes are important in cancer treatment for their passive targeting effect, which may lead to preferential accumulation in tumor tissue, but this phenomenon is not fully understood: Stealth liposomes are able to lodge in the interstitial spaces among tumor cells but, once in the tumor area, they locate in the extracellular fluid surrounding the tumor cell without entering it.” (Immordino, Dosio, & Cattel, 2006)
“Unfortunately, little is known of the kinetics of drug release from liposomes into the interstitial space: only the free drug can penetrate into the solid tumor, and it is difficult to determinate the ratio between free/liposome-encapsulated drug in the tumor extracellular fluid.” (Immordino, Dosio, & Cattel, 2006)
2010:
“An adjuvant for i.n.(Intranasal) inactivated influenza vaccine that is potent and safe for human use is still lacking.” (Saluja, et al., 2010)
Pharmacology:
1999:
2007:
"Paracetamol in overdose can cause renal failure. Most cases of renal failure have been reported to be in association with liver failure. However, isolated renal failure in the absence of liver damage has been reported. Whether or not this is due to a direct nephrotoxic effect of paracetamol or is secondary to hepatic failure is not fully known." (Pakravan, Bateman, & Goddard, 2007) The actual mechanism of nephrotoxicity in man is not fully understood.
Pharmacognosy
2008:
“It has recently been reported that the assay for aldose reductase inhibitors in ginger led to the isolation of five active compounds including 2-(4-hydroxy- 3-methoxyphenyl) ethanol and 2-(4-hydroxy-3-methoxyphenyl) ethanoic acid. These two named compounds were good inhibitors of recombinant human aldose reductase, with IC50 values of 19.2 ± 1.9 and 18.5 ± 1.1 lM, respectively. Furthermore, these compounds significantly suppressed not only sorbitol accumulation in human erythrocytes, but also lens galactitol accumulation in 30% of galactose-fed cataract rats, suggesting that protection against or improvement of diabetic complications could be achieved with a dietary supplement of either ginger or its extract containing aldose reductase inhibitors. However, more research into this is required, not only because of the limited experimental data, but also because of the lack of information on the effects of the chronic consumption of ginger in humans.” (Ali, Blunden, Tanira, & Nemmar, 2008)
“More studies are also required on the kinetics of ginger and its constituents and on the effects of their consumption over a long period of time.” (Ali, Blunden, Tanira, & Nemmar, 2008)
“Further trials in humans are required to determine the efficacy of ginger (or one or more of its constituents) and to establish what, if any, adverse effects are observed. However, double blind clinical trials are difficult to perform because the taste and smell of ginger are very pronounced.” (Ali, Blunden, Tanira, & Nemmar, 2008)
Bibliography
Ali, B. H., Blunden, G., Tanira, M. O., & Nemmar, A. (2008). Some phytochemical, pharmacological and toxicological properties of ginger (Zingiber officinale Roscoe): A review of recent research. Food and Chemical Toxicology , 409-420.
Benenson, Y. (2009). Biocomputers: from test tubes to live cells. Molecular bioSystems , 675-685.
Bielinsky, A. K., & Gerbi, S. A. (2001). Where it all starts: eukaryotic origins of DNA replication. Journal of Cell Science , 643-651.
Gilbert, D. M. (2001). Making Sense of Eukaryotic DNA Replication Origins. Science , 96-100.
Gonzalez, M. A., Tachibana, K. K., Laskey, R. A., & Coleman, N. (2005). Control of DNA replication and its potential clinical exploitation. NATURE REVIEWS | CANCER , 135-141.
Immordino, M. L., Dosio, F., & Cattel, L. (2006). Stealth liposomes: review of the basic science, rationale, and clinical applications, existing and potential. International Journal of Nanomedicine , 1 (3), 297-315.
Kobayashi, H., Kærn, M., Araki, M., Chung, K., Gardner, T. S., Cantor, C. R., et al. (2004). Programmable cells: Interfacing natural and engineered gene networks. PNAS , 8414-8419.
Law, J. A., & Jacobsen, S. E. (2010). Establishing, maintaining and modifying DNA methylation patterns in plants and animals. Nature Reviews Genetics , 11, 204-220.
Masai, H., Matsumoto, S., You, Z., Sugata, N. Y., & Oda, M. (2010). Eukaryotic Chromosome DNA Replication: Where, When, and How? Annual Review of Biochemistry , 89-130.
Nishitani, H., Taraviras, S., Lygerou, Z., & Nishimoto, T. (2001). The Human Licensing Factor for DNA Replication Cdt1 Accumulates in G1 and Is Destabilized after Initiation of S-phase. The Journal of Biological Chemistry , 44905-44911.
Pakravan, N., Bateman, D. N., & Goddard, J. (2007). Effect of acute paracetamol overdose on changes in serum and urine electrolytes. British Journal of Clinical Pharmacology , 824-832.
Rui, W. J. (1999). Regulation of eukaryotic DNA replication and nuclear structure. Cell Research , 163-170.
Rui, W. J. (1999). Regulation of eukaryotic DNA replication and nuclear structure. Cell Research , 163-170.
Saluja, V., Amorij, J. P., Roosmalen, M. L., Leenhouts, K., Huckriede, A., Hinrichs, W. L., et al. (2010). Intranasal Delivery of Influenza Subunit Vaccine Formulated with GEM Particles as an Adjuvant. The AAPS Journal , 12 (2), 109-116.
Simpson, M. L., Saylor, G. S., Fleming, J. T., & Applegate, B. (2001). Whole-cell biocomputing. TRENDS in Biotechnology , 317-323.
Soskine, M., & Tawfik, D. S. (2010). Mutational effects and the evolution of new protein functions. Nature Reviews Genetics , 11, 572-582.
More complex gene regulatory modules and interfaces need to be constructed to fully realize the capabilities of modular genetic control circuits. This could enable sophisticated processing capabilities, including event counting and signal integration. (Kobayashi, et al., 2004)
2009:
An entire molecular species is either in state Off (i.e. low concentration) or On (i.e. high concentration). An inherent difficulty with both interpreting and engineering digital reaction networks lies in the arbitrary definition of Off and On states. Clearly, concentrations can take any value between zero and infinity, and while defining the Off state is easy, doing so for the On state has to be justified. (Benenson, 2009) (On and Off represents to work or not to work respectively)
Predicting gene regulatory function from first principles still remains a major challenge. Moreover, even if such tools existed, they would not be able to tell us how to connect arbitrary transcription factor inputs to a specified output gene in a desired fashion – something we would expect from a programmable system. Engineering specified regulatory behaviors with arbitrary transcriptional regulators is therefore one of the main unsolved issues in synthetic biology and molecular computing. (Benenson, 2009)
It is somewhat surprising that despite solid theoretical foundations and intellectual maturity, actual implementation of large-scale transcriptional logic networks has been limited. Granted, many exciting synthetic networks with interesting properties relied solely on cascades of inverters or activators, or included negative and positive feedbacks. (Benenson, 2009)
There are also generic challenges pertaining to putting together and testing tens of gene components in a biological context. (Benenson, 2009)
There are intrinsic time delays for propagating the signal through multiple layers, as each stage requires both transcription and translation of protein92. Characteristic times required to accomplish this task depend on the host organisms, and non-surprisingly they are connected to other time scales of the hosts, in particular generation time. In applications where time is an issue, using more than three-four layers will make the network compute longer than it takes for the host cell to divide, leading to loss of resolution. Signal dissipation due to biological “noise”in deep cascades is another issue to consider. It is also interesting to note that nature's own transcriptional “computations” are rarely deeper than 2-3 layers, reflecting similar constraints. An alternative to deep cascades are wide and shallow circuits. Logic “normal forms” naturally lend themselves to such circuit architecture, but theoretical proposals to build such circuits79 have not been implemented yet. All the above challenges, however difficult, are well worth solving because transcription factors can be coupled to a large number of input peripherals. (Benenson, 2009)
In parallel, numerous technical issues will have to be solved, for example low-cost, rapid assembly of 20+ component circuits. Currently-available gene synthesis technologies are still costly and time-consuming. Another question pertains to the development of “debugging” tools, in other words, how will we know if such a complex network operates properly under all possible conditions? Yet another challenge is implanting these circuits in live cells, be it bacteria, yeast or mammalian cells. Each organism is different and each will attempt to bypass the newly introduced network. (Benenson, 2009)
Pharmaceutics:
2006: “The processes involved in delivery of these carriers (liposomes) and release of active agent, the variability of such processes (preferential accumulation of liposomes in the tumor area), and the degree to which the active agent is released into the tumor’s extracellular fluid or into tumor cells, are still unknown.” (Immordino, Dosio, & Cattel, 2006)
“Unfortunately, the effect of GM1 liposomes in prolonging half-life in bloodstream has been observed only in mouse models.” (Immordino, Dosio, & Cattel, 2006)
“A conclusive link has not yet been established between chemical and physical properties of PEG (polyethylene Glycol) and its ability to extend circulation lifetime. Although the accepted opinion is that PEG increases circulation longevity of drug carriers by reducing or preventing protein binding and/or by inhibiting cell binding/uptake, there is sufficient conflicting data to warrant a reassessment of the mechanism(s) by which surface grafted PEGs improve liposome properties.” (Immordino, Dosio, & Cattel, 2006)
“Stealth liposomes are important in cancer treatment for their passive targeting effect, which may lead to preferential accumulation in tumor tissue, but this phenomenon is not fully understood: Stealth liposomes are able to lodge in the interstitial spaces among tumor cells but, once in the tumor area, they locate in the extracellular fluid surrounding the tumor cell without entering it.” (Immordino, Dosio, & Cattel, 2006)
“Unfortunately, little is known of the kinetics of drug release from liposomes into the interstitial space: only the free drug can penetrate into the solid tumor, and it is difficult to determinate the ratio between free/liposome-encapsulated drug in the tumor extracellular fluid.” (Immordino, Dosio, & Cattel, 2006)
2010:
“An adjuvant for i.n.(Intranasal) inactivated influenza vaccine that is potent and safe for human use is still lacking.” (Saluja, et al., 2010)
Pharmacology:
1999:
2007:
"Paracetamol in overdose can cause renal failure. Most cases of renal failure have been reported to be in association with liver failure. However, isolated renal failure in the absence of liver damage has been reported. Whether or not this is due to a direct nephrotoxic effect of paracetamol or is secondary to hepatic failure is not fully known." (Pakravan, Bateman, & Goddard, 2007) The actual mechanism of nephrotoxicity in man is not fully understood.
Pharmacognosy
2008:
“It has recently been reported that the assay for aldose reductase inhibitors in ginger led to the isolation of five active compounds including 2-(4-hydroxy- 3-methoxyphenyl) ethanol and 2-(4-hydroxy-3-methoxyphenyl) ethanoic acid. These two named compounds were good inhibitors of recombinant human aldose reductase, with IC50 values of 19.2 ± 1.9 and 18.5 ± 1.1 lM, respectively. Furthermore, these compounds significantly suppressed not only sorbitol accumulation in human erythrocytes, but also lens galactitol accumulation in 30% of galactose-fed cataract rats, suggesting that protection against or improvement of diabetic complications could be achieved with a dietary supplement of either ginger or its extract containing aldose reductase inhibitors. However, more research into this is required, not only because of the limited experimental data, but also because of the lack of information on the effects of the chronic consumption of ginger in humans.” (Ali, Blunden, Tanira, & Nemmar, 2008)
“More studies are also required on the kinetics of ginger and its constituents and on the effects of their consumption over a long period of time.” (Ali, Blunden, Tanira, & Nemmar, 2008)
“Further trials in humans are required to determine the efficacy of ginger (or one or more of its constituents) and to establish what, if any, adverse effects are observed. However, double blind clinical trials are difficult to perform because the taste and smell of ginger are very pronounced.” (Ali, Blunden, Tanira, & Nemmar, 2008)
Bibliography
Ali, B. H., Blunden, G., Tanira, M. O., & Nemmar, A. (2008). Some phytochemical, pharmacological and toxicological properties of ginger (Zingiber officinale Roscoe): A review of recent research. Food and Chemical Toxicology , 409-420.
Benenson, Y. (2009). Biocomputers: from test tubes to live cells. Molecular bioSystems , 675-685.
Bielinsky, A. K., & Gerbi, S. A. (2001). Where it all starts: eukaryotic origins of DNA replication. Journal of Cell Science , 643-651.
Gilbert, D. M. (2001). Making Sense of Eukaryotic DNA Replication Origins. Science , 96-100.
Gonzalez, M. A., Tachibana, K. K., Laskey, R. A., & Coleman, N. (2005). Control of DNA replication and its potential clinical exploitation. NATURE REVIEWS | CANCER , 135-141.
Immordino, M. L., Dosio, F., & Cattel, L. (2006). Stealth liposomes: review of the basic science, rationale, and clinical applications, existing and potential. International Journal of Nanomedicine , 1 (3), 297-315.
Kobayashi, H., Kærn, M., Araki, M., Chung, K., Gardner, T. S., Cantor, C. R., et al. (2004). Programmable cells: Interfacing natural and engineered gene networks. PNAS , 8414-8419.
Law, J. A., & Jacobsen, S. E. (2010). Establishing, maintaining and modifying DNA methylation patterns in plants and animals. Nature Reviews Genetics , 11, 204-220.
Masai, H., Matsumoto, S., You, Z., Sugata, N. Y., & Oda, M. (2010). Eukaryotic Chromosome DNA Replication: Where, When, and How? Annual Review of Biochemistry , 89-130.
Nishitani, H., Taraviras, S., Lygerou, Z., & Nishimoto, T. (2001). The Human Licensing Factor for DNA Replication Cdt1 Accumulates in G1 and Is Destabilized after Initiation of S-phase. The Journal of Biological Chemistry , 44905-44911.
Pakravan, N., Bateman, D. N., & Goddard, J. (2007). Effect of acute paracetamol overdose on changes in serum and urine electrolytes. British Journal of Clinical Pharmacology , 824-832.
Rui, W. J. (1999). Regulation of eukaryotic DNA replication and nuclear structure. Cell Research , 163-170.
Rui, W. J. (1999). Regulation of eukaryotic DNA replication and nuclear structure. Cell Research , 163-170.
Saluja, V., Amorij, J. P., Roosmalen, M. L., Leenhouts, K., Huckriede, A., Hinrichs, W. L., et al. (2010). Intranasal Delivery of Influenza Subunit Vaccine Formulated with GEM Particles as an Adjuvant. The AAPS Journal , 12 (2), 109-116.
Simpson, M. L., Saylor, G. S., Fleming, J. T., & Applegate, B. (2001). Whole-cell biocomputing. TRENDS in Biotechnology , 317-323.
Soskine, M., & Tawfik, D. S. (2010). Mutational effects and the evolution of new protein functions. Nature Reviews Genetics , 11, 572-582.
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(Pages: 160, Price: 180 Rs.)
A book that will open your mind for more research
To Purchase this Book call at 0092-346-7585079
Pharmaceutical Chemistry:
2008:
“Mercury plays no known natural biological role in humans, and possible health effects of Mercury are a subject of dispute. Mercury itself is not toxic but most HTUMercury saltsUTH are, and some may be HTUcarcinogenicUTH, thus it was of interest to study the interaction of these metals in vitro to establish further scientific data.” (Khan, et al., 2008)
References:
Khan, M. F., Hashmat, Paracha, R. Z., Khan, H., Paracha, U. Z., Fazal-Ur-Rehman, et al. (2008). STUDY ON THE EFFECT OF MERCURY METAL ON THE CHEMICAL STATUS OF GSH IN AQUEOUS MEDIUM . Gomal University Journal of Research , 83-89.
2008:
“Mercury plays no known natural biological role in humans, and possible health effects of Mercury are a subject of dispute. Mercury itself is not toxic but most HTUMercury saltsUTH are, and some may be HTUcarcinogenicUTH, thus it was of interest to study the interaction of these metals in vitro to establish further scientific data.” (Khan, et al., 2008)
References:
Khan, M. F., Hashmat, Paracha, R. Z., Khan, H., Paracha, U. Z., Fazal-Ur-Rehman, et al. (2008). STUDY ON THE EFFECT OF MERCURY METAL ON THE CHEMICAL STATUS OF GSH IN AQUEOUS MEDIUM . Gomal University Journal of Research , 83-89.
