Explore further The protein process, a series of chemical reactions officially known as the mitogen activated protein kinase (MAPK) signal transduction cascade, plays a role in many cellular functions, including cell growth and development, cell division, and death. Inhibiting the cascade in tumor cells slows their growth and makes them easier to kill via chemotherapy.The MAPK cascade is the focus of much study because of its role in turning healthy cells into tumor cells and regulating tumor-cell functions. Because one drawback of chemotherapy is that it tends to kill normal cells along with malignant ones, interrupting the MAPK cascade in tumor cells could lead to cancer therapies that are more targeted and don’t induce as many side effects, which tend to leave cancer patients so sick.In this case, the researchers, from Harvard Medical School and National Chemical Laboratories, in India, designed nanoparticles from a biodegradable polymer material that chemically bond to a MAPK inhibitor, a molecule that disrupts the MAPK cascade. When tumor cells “ingest” the nanoparticles through the cell membrane, the particles release the inhibitor. In mice with melanoma, a cancer typically found in skin, this method slowed the growth of the tumors and increased the effectiveness of the chemotherapy drug they were given, cisplatin, which is used to treat most cancers. With further research, this work could lead to more successful chemotherapy treatments in humans.Notably, this work is the first published report of a MAPK inhibition method that has been combined with nanoparticle-based tumor targeting, another area that shows promise for cancer treatments. The research opens a door to the use of nanoparticles and other nanostructures as vehicles for blocking or interrupting the processes that cause tumors to grow.For more information: Sudipta Basu, Rania Harfouche, Shivani Soni, Geetanjali Chimote, Raghunath A. Mashelkar, and Shiladitya Sengupta (April 21, 2009) Proc. Natl. Acad. Sci. USA, 10.1073/pnas.0902857106© 2009 PhysOrg.com Citation: Nanoparticles May Help Optimize Chemotherapy (2009, May 6) retrieved 18 August 2019 from https://phys.org/news/2009-05-nanoparticles-optimize-chemotherapy.html A more direct delivery of cancer drugs to tumors
(PhysOrg.com) — With advancements in genetic engineering, researchers say that it may soon be possible to breed farm animals that don’t feel pain. The suggestion has sparked controversy on whether denying animals the ability to feel pain is inhumane itself, even if it does limit the amount of suffering the animals endure when raised at factory farms. This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no part may be reproduced without the written permission. The content is provided for information purposes only. Researchers say that breeding pain-free farm animals is less of a technological issue and more of an ethical issue. Image credit: Guido Gerding. Explore further In recent decades, humans have been consuming more and more meat. Since the 1960s, human consumption of meat has increased by 50 percent, most of it coming from factory farms. Despite demands by animal rights groups for better treatment of farm animals, eliminating animal suffering seems to be an unrealistic goal. For example, chickens often have part of their beaks removed without anesthesia to prevent them from pecking each other. If factory farms can’t be persuaded to raise animals in humane environments, then maybe it’s time to provide the animals with an inborn defensive mechanism of their own.The solution may not be ideal, but, as Adam Shriver, a philosopher at Washington University in St. Louis says, “If we can’t do away with factory farming, we should at least take steps to minimize the amount of suffering that is caused.”In recent years, scientists have made progress in manipulating the molecular and genetic bases for pain. A recent study found that mice that lack the Nav1.7 gene are less sensitive than normal mice to heat and pressure. Possibly, farm animals that lack such a gene would also suffer less under factory farm conditions. In another study, scientists have engineered mice that lack specific enzymes and genes in the anterior cingulate cortex (ACC). This alteration enabled the animals to still sense pain, but not feel it as an unpleasant sensation. By still feeling physical sensation, the animals could avoid unintentionally injuring themselves, which often happens in individuals who are born without the ability to feel pain at all.But there are other alternatives to pain-free animals, one of which is producing meat in vitro. Although not fully developed yet, the procedure involves growing animal muscle cells that could be used in processed meats such as chicken nuggets and fish sticks. However, lab-grown animal cells are currently costly, since they require expensive nutrients, and the technology would need to be scaled up in order to be profitable. Besides eliminating animal suffering, this option could also eliminate the other negative side effects of factory farms, including the large amounts of waste and greenhouse gases that are generated.via: New Scientist© 2009 PhysOrg.com Citation: Would Pain-Free Animals Make a More Humane Hamburger? (2009, September 3) retrieved 18 August 2019 from https://phys.org/news/2009-09-pain-free-animals-humane-hamburger.html PETA offers $1 million for fake meat
Citation: Scientists Use Inkjet Printer to Manipulate Genes in New Ways (2009, October 5) retrieved 18 August 2019 from https://phys.org/news/2009-10-scientists-inkjet-printer-genes-ways.html This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no part may be reproduced without the written permission. The content is provided for information purposes only. Explore further Daniel Cohen and Michel Maharbiz of the University of California, Berkeley, along with Roberto Morfino of the École Polytechnique Fédérale de Lausanne in Switzerland, have published their new method in a recent issue of PLoS ONE. “On an engineering level, we developed an extremely low-cost, user-friendly system that any biology lab can use to explore spatiotemporal control of biological systems,” Cohen told PhysOrg.com. “On a scientific level, we demonstrated that, by controlling the position and timing of chemical dosing in a biological system, we can manipulate arbitrary genetic circuits into behaving like more complex morphogenetic circuits, which are the genetic circuits that regulate pattern formation, such as where our head is relative to our feet and why we have five fingers.”In their study, the researchers used a commercial-grade Epson R280 inkjet printer to print patterns of lactose and glucose onto an agar gel culture of E. coli in order to regulate the pathway called the lac operon. As the scientists explained, lactose acts as an inducer, while glucose acts as an inhibitor in the bistable lac operon system. The lac system has four states. It can be effectively off if there is no lactose or glucose. If there is glucose but no lactose, the system is also off. If there is glucose and lactose, the system is low-on. If there is lactose and no glucose, the system is full-on. The reason is that glucose provides more energy than lactose so it is better not to waste resources eating lactose if glucose is around. In their new method, the researchers used a syringe pump to manually inject the lactose and glucose “inks” into the printer’s color reservoirs. The printer functions completely normally, but prints the injected solutions rather than ink. The Epson R280 also has the ability to print on rigid substrates, enabling the researchers to use normal compact discs (CDs) as substrates. Before printing, the scientists first milled 800-micron-deep wells directly into the surface of the CDs, into which they transferred the E. coli cultures. Finally, they used Adobe Photoshop to create specific patterns using the inks, and then to print them directly into the wells. (PhysOrg.com) — With recent advances in biochemistry, researchers can control the circuitry in a developing cell, thereby influencing cells to develop into specific phenotypes. Taking a step forward in this area, researchers have recently demonstrated a new technique to control gene expression in two dimensions over time, which has not previously been demonstrated. And they have done so using a slightly modified $100 inkjet printer. The researchers took photos of the E. coli cultures with a digital camera 15 hours after printing. They could see the patterns of lactose and glucose where they had printed in dark and light areas, respectively, due to the state of the lac operon. The bistability of the lac operon allowed for the generation of sharp gene expression boundaries, but the scientists also observed interesting dynamical behavior at boundaries between glucose and lactose areas. Overall, using an inkjet printer to control cellular behavior could give researchers a versatile, low-cost, and open-source tool for a variety of applications in controlling gene expression. “Fundamental science relies on the ability to manipulate specific pathways in a controlled fashion,” Cohen explained. “This allows us to learn more about the behavior of those pathways, and precise control of genetic activity is often the only way to answer questions such as what genes are responsible for what activities. On a more bio-engineering level, controlling gene expression will ultimately allow us to regulate the behavior of biological systems. Techniques such as medical gene therapy rely on this concept, while tissue engineering could greatly benefit from the ability to specify which genes are active in a given place at a given time.”In addition, synthetic biologists are already building synthetic multicellular constructs, and could use this new method to influence the development of patterns. “Apart from basic science, controlling genetic activity is of enormous importance in synthetic biology,” Cohen said. “For instance, people like Dr. Jay Keasling are using custom-made genetic circuits to control the production of artemisinin (an anti-malarial drug) in bacteria. Similarly, medical tissue engineering relies heavily on our ability to tell cells what to do. Sometimes the cells naturally do what we want, but other times we need to be able to specify that a stem cell differentiates into a certain lineage, or that cells in a particular area start to form blood vessels. This type of control can be achieved in many ways, one of which is through direct control of genetic activity.” More information: Daniel J. Cohen, Roberto C. Morfino, Michel M. Maharbiz. “A Modified Consumer Inkjet for Spatiotemporal Control of Gene Expression.” PLoS ONE. September 2009, Volume 4, Issue 9, e7086. www.plosone.org/article/info%3 … journal.pone.0007086Copyright 2009 PhysOrg.com. All rights reserved. This material may not be published, broadcast, rewritten or redistributed in whole or part without the express written permission of PhysOrg.com. Scientists have used an Epson R280 inkjet printer to dynamically control gene expression in two dimensions. Image credit: Cohen, et al. Bone-cell control of energy generation is regulated by the protein Atf4
SpaceX Plans Reusable Seven Person Capsule In order to get to Mars, they need to be able to transport a significant amount of cargo and people and this, according to Musk, will require a fully reusable rocket and they are working to make their Falcon 9 rocket just that. The Falcon 9 rocket is designed to generate 1700 metric tons of thrust which would make it easily capable of transporting satellites, cargo and humans.Unfortunately creating a fully reusable rocket is not proving easy. With just 0.3 percent of the Falcon 9 launch cost being propellant, the target is to create a complete launch system that is fully reusable in order to reduce the cost of launches. So far engineers have not been able to provide the level of protection needed to be able to reuse the first and second stages.On paper, they have created something that they hope will prove effective. They are looking at restarting the engines in order to slow down the first stage and shed some of the velocity. However, in order to do this, they have to look at payload loss of fuel in orbit, better thermal shielding and increased structural margins for recovery.Musk announced plans to demonstrate a new Falcon Heavy rocket in the later part of 2012 or the first part of 2013. This rocket will be capable of delivering 10 to 15 metric tons, but they hope to make it capable of delivering 50 metric tons and be fully reusable in the future.They are discussing a project with NASA to use their Dragon capsule and Falcon rocket for an exploratory mission to Mars and they hope to be ready for this mission by 2018. At an August conference hosted by the American Institute of Aeronautics and Astronautics, SpaceX CEO Elon Musk revealed plans for how they hope to get humans on Mars within the next 20 years. Explore further Citation: SpaceX plans to get humans on Mars (2011, August 3) retrieved 18 August 2019 from https://phys.org/news/2011-08-spacex-humans-mars.html © 2010 PhysOrg.com This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no part may be reproduced without the written permission. The content is provided for information purposes only.
The name they’ve given it comes from pampas, the name of the open plains where the skull was found and the word for killer. Biccai comes from Bicca, the last name of the man who owned the land.Because they have only a skull to work with, the team has had to use the remains of other similar ancient remains found in South Africa, Russia and China to deduce what the reptile might have looked like. They believe it falls into the class Dinocephalian therapsid (reptiles with some mammal characteristics) and was about the size of a leopard, cold blooded, and had powerful jaws that enabled it to rip flesh from prey it very likely caught. Also, they believe it lived somewhere around 265 million years ago, putting it before the dinosaurs, which meant it also lived in a time when the continents were joined which explains how it could be so similar to other therapsids found in Africa and Asia.The team also believe Pampaphoneus biccai lived in herds because of footprint finds of relatives in South Africa. Scientists hope that the new find will help in plotting the migration of the ancient therapsids, which may help buffer arguments about the geography of the ancient continent known as Pangeae. More information: Carnivorous dinocephalian from the Middle Permian of Brazil and tetrapod dispersal in Pangaea, PNAS, Published online before print January 17, 2012, doi: 10.1073/pnas.1115975109AbstractThe medial Permian (∼270–260 Ma: Guadalupian) was a time of important tetrapod faunal changes, in particular reflecting a turnover from pelycosaurian- to therapsid-grade synapsids. Until now, most knowledge on tetrapod distribution during the medial Permian has come from fossils found in the South African Karoo and the Russian Platform, whereas other areas of Pangaea are still poorly known. We present evidence for the presence of a terrestrial carnivorous vertebrate from the Middle Permian of South America based on a complete skull. Pampaphoneus biccai gen. et sp. nov. was a dinocephalian “mammal-like reptile” member of the Anteosauridae, an early therapsid predator clade known only from the Middle Permian of Russia, Kazakhstan, China, and South Africa. The genus is characterized, among other features, by postorbital bosses, short, bulbous postcanines, and strongly recurved canines. Phylogenetic analysis indicates that the Brazilian dinocephalian occupies a middle position within the Anteosauridae, reinforcing the model of a global distribution for therapsids as early as the Guadalupian. The close phylogenetic relationship of the Brazilian species to dinocephalians from South Africa and the Russian Platform suggests a closer faunistic relationship between South America and eastern Europe than previously thought, lending support to a Pangaea B-type continental reconstruction.Press release Because Brazil is covered in so much vegetation, it’s difficult to find sites. Google Earth allows such researchers to see patches of open areas, so upon finding one, that’s where the team went. Afterwards, they took pictures of their find and sent them back to their professor at the University of Witwatersrand, in South Africa, which is a sort of hotbed for fossil study due to the large numbers of specimens found in an area nearby known as the Karoo. After much study, the two finders of the fossil and a team from Witwatersrand, will have their findings published in the Proceedings of the National Academy of Sciences, and report that they believe the skull once belonged to a creature called Pampaphoneus biccai and is related to an ancient reptile found in South Africa called Australosyodon. Pampaphoneus biccai, illustration. Image credit: Voltaire Neto / University of Witwatersrand Journal information: Proceedings of the National Academy of Sciences
(Phys.org)—Synthetic biology is a multi-disciplinary field that applies engineering techniques to biological systems. While the foundations of synthetic biology were laid in the 1990s with the burgeoning of genomics and automated sequencing, synthetic biology as a discipline, emerged in the early 2000s with the development of simple gene regulatory circuits. Since then, the field has grown beyond making simple circuits to developing diagnostic tools. More information: Shimyn Slomovic et al. Synthetic biology devices for in vitro and in vivo diagnostics, Proceedings of the National Academy of Sciences (2015). DOI: 10.1073/pnas.1508521112AbstractThere is a growing need to enhance our capabilities in medical and environmental diagnostics. Synthetic biologists have begun to focus their biomolecular engineering approaches toward this goal, offering promising results that could lead to the development of new classes of inexpensive, rapidly deployable diagnostics. Many conventional diagnostics rely on antibody-based platforms that, although exquisitely sensitive, are slow and costly to generate and cannot readily confront rapidly emerging pathogens or be applied to orphan diseases. Synthetic biology, with its rational and short design-to-production cycles, has the potential to overcome many of these limitations. Synthetic biology devices, such as engineered gene circuits, bring new capabilities to molecular diagnostics, expanding the molecular detection palette, creating dynamic sensors, and untethering reactions from laboratory equipment. The field is also beginning to move toward in vivo diagnostics, which could provide near real-time surveillance of multiple pathological conditions. Here, we describe current efforts in synthetic biology, focusing on the translation of promising technologies into pragmatic diagnostic tools and platforms. Shimyn Slomovic, Keith Pardee, and James J. Collins of MIT and Harvard discuss the current trends in synthetic biology to make diagnostic tools, and what additional hurdles must be overcome before these methods can be applied in the field or in the clinical setting. Their article is part of a special hundredth anniversary series in the Proceedings of the National Academy of Sciences commemorating exceptional research published in the journal over the last century.The rational design of diagnostic tools in synthetic biology uses natural regulation and detection systems to design sensors. Ideally, these sensors are selective, sensitive, and provide some kind of output, such as fluorescence or a color change, when it has detected the target cell, environmental cue, or pathogen. Slomovic, Pardee, and Collins discuss three broad categories of synthetic biology-based diagnostic tools: whole-cell biosensing, in vitro diagnostics, and in vivo diagnostics.Whole-cell biosensingMicroorganisms can be employed as a kind of biosensor. One well-known example is photosynthetic cyanobacteria incorporated into hardware. The cyanobacteria are redox active. Electron transfer through the hardware will produce a current, but herbicides quench its redox activity. The lack of current serves as an indicator for the presence of herbicides in places such as natural water reservoirs. More recent research involves tailoring microorganisms using genetic engineering. Engineering methods allow scientists to design bacteria that are selective for a particular substance. For example, bacteria have been engineered to detect arsenic in water. These genetically engineered bacterial cells have been integrated into circuits and other mechanical components to produce a hybrid device. However, hybrid devices have lost popularity, giving way to plate readers which have a higher throughput. RNA-based biosensing can detect metabolites or RNA sequences that are specific to a particular disease. RNA biosensing works by releasing stalled RNA translation using a synthetic piece of RNA that contains a complementary portion of the target sequence. One of the difficulties with this technique, however, is that the RNA sensing portions are confined within the bacterial cell and are not accessible to the external environment. Paper-based synthetic gene networks could enable rapid detection of Ebola and other viruses In vitro diagnosticsBacteriophages are nature’s bacteria sensors. They are viruses that home in on particular bacteria and infect them. Engineered bacteriophages are relatively inexpensive to make and can be designed to provide output indicators, such as bioluminescence, when it has detected the presence of a particular bacterial strain. Bacteriophages have been used both as sensors and as alternatives to antibiotics. For example, phages allow scientists to detect the presence of bacteria associated with the bubonic plague in a human blood sample in a matter of hours.Paper-based diagnostics are a cheap, mobile method that shows promise for eventual field use. Using commercially available bacterial or mammalian transcription/translation systems, scientists are able to freeze-dry these systems on to paper or other porous materials. These systems target certain RNA sequences in a similar way to the RNA-based biosensing, mentioned above, but the circuitry is on paper rather than within the cell. The system becomes active when rehydrated, allowing the freeze-dried material to be easily transported. Recent tests with an Ebola virus disease detection system used color-changing enzymes for easy output. In vivo diagnosticsReal-time biosensing is attractive for monitoring changes in the organism’s internal environment. This can be done with engineered bacteria that are administered to the organism. One example is the use of engineered E. coli to monitor the gut microbiome. In mouse studies, E. coli. were engineered to detect and record exposure of the gut microbiome to a particular drug.Mammalian cells can also function as in vivo biosensors, and they have the added benefit of possibly serving as both the sensor and the therapy. These cells utilize synthetic gene networks that can either change or monitor the organism’s cellular environment. Additionally, cellular biosensing allows the synthetic circuit to be isolated from the environment but also able to interact with it.One way that mammalian cells have been used for diagnostics is to monitor the expression profiles of certain cells. Cells express, or “turn on”, some genes but not others. The particular set of genes that are turned on provides an expression profile. Some cancer cells, cells that have been infected by a virus, or cells whose immune system is malfunctioning (autoimmune) have different expression profiles from normal cells. These cells can be targeted and identified using engineered mammalian cells. This has the added benefit of potentially destroying the diseased cell either by turning on the cell’s self-destruct genes or by drug targeting.Unfortunately, the biggest difficulty with in vivo diagnostics is delivering the engineered cell or synthetic genetic construct to the right place. Slomovic, Pardee, and Collins point out that this is where the field of nanobiotechnology comes into play. Recent research shows that some nanoparticles will home in on certain cells types, and others have been looking at lipid-based vesicles as another possibility for targeted delivery.Slomovic, Pardee, and Collins point out that “success in synthetic biology will continue to be found at the interfaces between disciplines.” Synthetic biology, while still a relatively new field, draws from years of work in genetics, microbiology, engineering, and nanotechnology, and by combining these fields, researchers have been able to make formidable progress in biosensing and in vitro and in vivo diagnostics. Explore further This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no part may be reproduced without the written permission. The content is provided for information purposes only. Citation: Diagnostic tools using synthetic biology (2015, December 3) retrieved 18 August 2019 from https://phys.org/news/2015-12-diagnostic-tools-synthetic-biology.html Journal information: Proceedings of the National Academy of Sciences © 2015 Phys.org
© 2016 Tech Xplore Explore further Techniques involving the use of terahertz radiation have been evolving in recent years, leading to devices able to see through materials to take pictures of what lies beneath. Because T-rays are less energetic than X-ray or gamma rays, they are less likely to cause damage. That has made them ideal for use in detecting hidden images behind paintings and discovering defects in panels used on space craft. But there have been two problems with using T-rays more widely, the first is that it costs a lot, and the second is that it cannot be used in applications smaller than its wavelength, which has held back its resolution abilities. In this new effort, the researchers have not found a solution for the first problem but have dramatically improved the second.To improve the resolution, the team illuminated an object hidden behind a silicon wafer with two different sources, one of them was a standard terahertz beam, and the other was light that sent pulses of different dark and light patterns onto the object under study. The patterns that were projected onto the wafer caused part of it to become conductive, which meant the T-rays could not pass through them. Thus the T-rays were able to easily pass through the wafer but were then scattered as they struck the object hidden on the other side. Using a pixel detector allowed for recording the T-rays that made their way through, allowing for image creation.Using the technique, the researchers report that they were able to detect cracks in a circuit board affixed to the opposite side of a wafer, at approximately double the resolution of existing terahertz imaging techniques. They believe their technique could prove useful in the microelectronics industry, and perhaps in medicine, as it might be used to detect very tiny tumors. This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no part may be reproduced without the written permission. The content is provided for information purposes only. More information: R. I. Stantchev et al. Noninvasive, near-field terahertz imaging of hidden objects using a single-pixel detector, Science Advances (2016). DOI: 10.1126/sciadv.1600190AbstractTerahertz (THz) imaging can see through otherwise opaque materials. However, because of the long wavelengths of THz radiation (λ = 400 μm at 0.75 THz), far-field THz imaging techniques suffer from low resolution compared to visible wavelengths. We demonstrate noninvasive, near-field THz imaging with subwavelength resolution. We project a time-varying, intense (>100 μJ/cm2) optical pattern onto a silicon wafer, which spatially modulates the transmission of synchronous pulse of THz radiation. An unknown object is placed on the hidden side of the silicon, and the far-field THz transmission corresponding to each mask is recorded by a single-element detector. Knowledge of the patterns and of the corresponding detector signal are combined to give an image of the object. Using this technique, we image a printed circuit board on the underside of a 115-μm-thick silicon wafer with ~100-μm (λ/4) resolution. With subwavelength resolution and the inherent sensitivity to local conductivity, it is possible to detect fissures in the circuitry wiring of a few micrometers in size. THz imaging systems of this type will have other uses too, where noninvasive measurement or imaging of concealed structures is necessary, such as in semiconductor manufacturing or in ex vivo bioimaging. (Phys.org)—A team of researchers with members from the University of Exeter, the University of Glasgow and QinetiQ, all in the U.K. has found a way to effectively double the resolution offered by near-field terahertz imaging. In their paper published in the journal Science Advances, the team describes how the technique works and some of the applications that might be bettered through its use. A terahertz image taken with the newly developed, non-invasive sub-wavelength terahertz imaging setup. The image size is 2x2mm and the structure was hidden behind a silicon wafer. Credit: Stantchev et al. Citation: New technique doubles resolution of near-field terahertz imaging (2016, June 6) retrieved 18 August 2019 from https://phys.org/news/2016-06-technique-resolution-near-field-terahertz-imaging.html Light-powered 3-D printer creates terahertz lens Journal information: Science Advances
Tagore International School in the Capital opened their doors for students from Pakistan in a student exchange program called Students Exchange For Change-II, initiated by Indian NGO Routes 2 Roots and The Citizens Archive of Pakistan (CAP). The aim of the program was to was to encourage friendship between school students across the border. The participants aged between 10 and 14 years were a part of the initiative.During the programme the children screened a short audio-video clip about their parents, grandparents and their different cultures. These students have been exchanging letters and post cards for 16 months under the program. Also Read – ‘Playing Jojo was emotionally exhausting’This workshop aims to bring the nations closer as they to get familiar with shared histories, traditions and stories. The children were overwhelmed to learn the past history of their ancestor as they were once all one and united.’This program is very close to my heart and has given me immense satisfaction to see the growing friendship between the children. It is a pleasure to see the growing understanding between the students, change in their perceptions and reducing biased thinking, which helps them to dream of a brighter future,’ said Tina Vachani, founder of Route 2 Route.
These bear operators are said to have created huge short positions in the stock market over the past few days, which means they were betting on a fall in the market values.It is suspected that these operators could have been behind wide-spread rumours last week that authorities were all set to ban Participatory Notes (P-Notes), which are used by overseas HNIs, hedge funds and other foreign institutions to invest in Indian markets through registered overseas entities. Also Read – I-T issues 17-point checklist to trace unaccounted DeMO cashWhile there have been long-standing concerns about possible misuse of Offshore Derivative Instruments, or P-Notes, for money laundering and other such purposes, these instruments are also used widely by genuine investors looking to save on time and costs attached with direct investments.While no clampdown has taken place against P-Notes, capital markets regulator Sebi on Monday reiterated its regulatory framework for such investments by stating that the foreign investors need to ensure compliance with all necessary norms before issuing such notes. Also Read – Lanka launches ambitious tourism programme to woo Indian touristsHowever, Sebi’s move was taken as further regulatory tightening on P-Notes, resulting in a significant plunge in stock market indices on Tuesday.Sources, however, said that a preliminary analysis of trade data for Tuesday, the first trading session after Sebi’s latest circular, shows that the sale of shares were mostly conducted by domestic investors and not the foreign entities.As per the provisional stock exchange data, the FPIs (Foreign Portfolio Investors) made gross purchase of shares worth over Rs 13,000 crore on Tuesday and were net buyers to the tune of about Rs 1,200 crore. On the other hand, the large domestic investors were net sellers on the day to the tune of about Rs 1,000 crore.While no conclusive evidence has so far come to the fore against any particular group of entities, the market authorities are in the process of analysing trade data for all short-positions over the past few days, while they are also tracking the trading pattern of some suspected bear operators.As per the latest Sebi circular, which has no changes in the existing regulations that FPIs need to comply with while issuing ODIs, the existing ODI positions will be allowed to continue till expiry if they are not in compliance with the relevant provisions of FPI Regulations.Any additional issuance, renewal or rollover of such non-compliant positions would not be permitted, Sebi had said.However, this provision also forms part of the existing norms that have already been in place, sources said, while adding that the latest circular was more in clarificatory in nature.The investments through P-Notes rose to nearly seven-year high of over Rs 2.65 lakh crore at the end of October 2014.