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  • Sagar Bachhav added an answer in Cancer Treatment:
    How can I calculate the synergistic effect between drugs and cells in cancer killing assays?

    Does anyone know if it's possible to calculate the synergistic effect of drugs and cells in cancer treatment. The current available formulas only apply to the combination of drugs but not drugs and cells.

    Sagar Bachhav

    Dear Mauro,

    Not actively working on this  but as per my understanding, you can use the method available for drug+drug...

    Synergism tells you that the combined effect is greater than that of predicted individual effects. And synergism helps in reducing dose and thereby toxicity associated. So two things are important ...dose and effect.

    Drug should not be necessarily a chemical compound..so your Chimeric Antigen Receptors (CAR-T cells) T-calls is DRUG here and you must be using it at particular concentration. So you have DOSE (ED50) for that. Don't confused yourself in terminologies of cell-drug...

    You may also refer attached research article. you may have already refereed this...!

    Hope your doubts are somewhat cleared.

    Best luck


  • Barbora Kubíková added an answer in Neolithic Archaeology:
    What to do with the clay balls in Late Neoltihic sites??

    I would be very grateful if anybody was interested in my research about the clay balls - rounded handy sized clay objects. I am trying to distinguish among them, sort them according to the dimensions, weight and shape. I will compare them with the artefacts assigned as sling balls from the sites where they are attested. If anybody has a good database (e.g.. xls data sheets) of clay balls from Halafian sites and wants to share it, please contact me.

    I need this for my master thesis.


    Barbora Kubíková

    Dear Ernestine,

    that would be wonderful because I was searching the Internet but I cannot access Sitagroi and in my library we do not have this book. I would be very glad if you scan for me those pages. My email is barbora.kubikova.89@gmail.com

    Thank you,


  • Jan Matthias Peter added an answer in Zircon:
    Does anyone have information about hydrozircon occurrence?

    In Czech Republic, this form of zircon is a component of the U-Zr assemblage on the peneconcordant stratiform deposits in sandstones of northern Bohemia. Characteristic of this zircon is its metacolloidal to gel nature and other physical properties (low specific gravity, low aggregate hardness, and low refraction). It is so far known only from a few localities all over the world such as Wind River Formation in Wyoming. Does anyone know of a similar type of mineralization?

    Jan Matthias Peter

    here is a paper on hydrothermal zircons: M. Toscano a, E. Pascual a,⁎, R.W. Nesbitt b, G.R. Almodóvar a, R. Sáez a, T. Donaire a, 2014, Geochemical discrimination of hydrothermal and igneous zircon in the Iberian Pyrite Belt, Spain. ore geology reviews 56, pp301-311

  • Shannon O'Sullivan asked a question in LDH Assay:
    How do I standardize the LDH activity to protein content per well for my LDH assay?

    I am going to be running a series of cytotoxic assays one being LDH assay which I have not done before. I have been told that I need to standardize the LDH activity to protein content per well but I am unsure on how I go about doing this any suggestions? 

  • Rajeeb Dey added an answer in Cost Control:
    How can I differ optimal guaranteed Cost Control with optimal control?

    How can I differ optimal guaranteed Cost Control with optimal control?

    Yurong Liu, Department of Mathematics, China.

    Rajeeb Dey

    The answer seems interesting @ Prasanta...but following things may be highlighted to have a clear distinctions..

    1. Do you mean the control law in optimal control is not computed under closed loop?

    2. Do you mean optimal control is not robust?

    3. Do you mean Gauranteed cost control is not optimal?

    4, Can you not design Guaranteed cost control using the the PI mentioned like IAE, ITSE etc...?

    5. Can guaranteed cost control problem handle nonlinearity in the system?

  • Dipak Kathayat asked a question in Small Molecules:
    Novel non antibiotic compounds?

    I am doing small molecule screening for mitigation of effect of different micro organisms.Sharing of idea will be highly appreciated.

  • Bartosz Rustecki added an answer in Tetracaine:
    Does anybody have any experience in introducing the A&E department to LAT (lidocaine, adrenaline, tetracaine)gel as a topical anaesthetic in children?

    Does anybody have any experience in introducing the A&E department to LAT (lidocaine, adrenaline, tetracaine) gel as a topical anaesthetic in children?

    We are hoping to trial LAT gel in our department for children with wounds usually requiring conscious sedation or GA to close lacerations, but also to thoroughly clean large abrasions. As we know the former is a real challenge in the DGH and the latter can be very painful, especially in children, even with the gentlest 'paeds nurse' touch!


    Bartosz Rustecki

    Lidocaine gels and other simillar penetrate skin up to 5 mm. It works with vaccine injections with small children. Also mostly for inplementation intrevenous cathtters. But for wounds it will be probably not enought.

  • Lisa R. Keyes asked a question in Incubation:
    What is the best kit or assay to detect complement factor H function?

    I am looking for a kit, or well described assay to determine the functionality of complement factor H. I have seen brief protocols involving incubating different amounts of factor H with Facto I and C3b on ice, then incubating at 37*C, then running on SDS-PAGE. Is there a kit that has the Factor I and C3b available? Or do I need to purchase everything separately? If there is no kit for this, do you know of a well cited protocol anywhere?

  • Stephen Angudubo added an answer in Choice Experiments:
    How can I estimate willingness-to-pay (WTP) for cassava seed using choice experiment of attributes using STATA?

    I have data from choice experiment of cassava planting material and other socio-economic characteristics of the households. I need to establish the attributes preferred including the levels; estimate the willingness to pay and potential demand from choice experiment of attributes of cassava planting material such as yield, and taste and all tied to a price, where the respondent have chosen yes or no depending on the view of attributes or opted out (no to both alternatives). How can estimate this with stata 13? Thanks

    Stephen Angudubo

    Thanks Zahra, an example will be helpful

  • Jan Holmgren added an answer in Cognitive Systems:
    Is Chalmers' so-called "hard problem" in consciousness real?

    In his 2014 book "Consciousness and the Brain: Deciphering How the Brain Codes Our Thoughts" Stanislas Dehaene wrote "Chalmers, a philosopher of the University of Arizona, is famous for introducing a distinction between the easy and the hard problems. The easy problem of consciousness, he argues, consists in explaining the many functions of the brain: how do we recognize a face, a word, or a landscape? How do we extract information form the senses and use it to guide our behavior? How do we generate sentences to describe what we feel?

    “Although all these questions are associated with consciousness,” Chalmers argues, “they all concern the objective mechanisms of the cognitive system, and consequently, we have every reason to expect that continued work in cognitive psychology and neuroscience will answer them. By contrast the hard problem is the “question of how physical processes in the brain give rise to subjective experience … the way things feel for the subject. When we see for example, we experience visual sensations, such as that of vivid blue. Or think of the ineffable sound of a distant oboe, the agony of an intense pain, the sparkle of happiness or the meditative quality of a moment lost in thought … It is these phenomena that poses the real mystery of the mind”."

    Stanislas Dehaene's opinion is "that Chalmers swapped the labels: it is the “easy” problem that is hard, while the “hard” problem just seems hard because it engages ill-defined intuitions. Once our intuition is educated by cognitive neuroscience and computer simulations, Chalmers’ “hard problem” will evaporate".

    Personally, I agree with Stanislas Dehaene's opinion.

    Jan Holmgren

    Alfredo: “Dear Jan, it seems there is something missing in our communication - the concept of infinity we are using is probably different. I am not proposing to build a continuum by means of summing discrete parts. This idea is probably wrong. I am proposing that the phenomenal world with its qualitative subjective states is composed by the combination of elementary forms that eternally exist in Nature as potentialities. For instance, when you feel that "happy madness" (as the title of the song says) you feel a combination of "happiness" and "madness" in the same way that a musical chord is made of musical notes. What I am proposing as infinite is the number of possible combinations. Each individual can combine such elementary forms in a singular way that never happened before in the history of the universe (or multiverse).”

    Jan: Dear Alfredo, you aim to improve “the scientific worldview” by the introduction of a mediating aspect (the informational) between materialism and idealism (“2pp” between “3pp” and “1pp”), thus making place for consciousness in a scientific setting. It may be productive in science, but to me the ultimate cosmology is really not credible.

    For me a science of consciousness, to be credible, should fully accept and express the human predicament: that we humans ultimately are fully and solely dependent on our conscious experiences for absolutely everything we know of. Thus, in principle we should attempt to start with consciousness and reason from there, while you start with materialism basing your worldview on the difficult concept “the totality of possible states of Nature”.

    I understand that ultimate limits for human insights are not palatable in science, but please consider that perhaps something like 95% of the universe is still completely unknown. A more realistic concept to start from would be “the totality of possible conscious experiences”. Science is a limited part of that, with certain defining characteristics. Potentialities will naturally be thought of as objectified (evolved or learned) in human brains, discrete and consciously experienced when actualised, while the universe, including our brains, can be thought wholly continuous.

    This more realistic cosmology of course does not in any way disqualify scientific work, it only warns against too far reaching extrapolations in abstraction.

  • Hina Hussain added an answer in Infrared Spectroscopy :
    Any advice in calculating IR absorption ratio?

    Can anybody help me calculating the area under the curve but this area is not simple this is area which is presented in the picture attached and the arrows shows both area from the 0 absorption to the start of signal and then the curve of the signal.... can anybody help me calculating it using origin or anyother software ?

    Hina Hussain

    Thank you very much Arther Markus and Jean Rene Grezes...... 

  • Henri Cloetens added an answer in Insulation:
    How effective is vacuum insulation at high temperatures?

    Hi All,

    I am trying to assess feasibility to store energy as heat. Now, not to loose too much, it needs to be insulated, by eg a double-walled steel tank, with vacuum between both tanks, and filled with some cheap insulation material, like basalt wool.

    Can anybody help me how efficient this would be at hot ?. The highest temperature possible with cheap steel is about 500 degC.

    Best Regards,


    Henri Cloetens

    Hello Robert,

    Yes, this is very true that the vacuum only stops the gas conduction. To stop the radiative heat transfer, there needs to be a fill, the propose fill is some cheap material like basalt wool (rockwool.) The question is, if somebody did this before, what result can be expected ?.

  • Darioush Khodabakhshi asked a question in Ulcer:
    What is the effect of collagen on diabetic ulcers?

    what is the effect of collagen on diabetic ulcers?

  • Jean François Cart added an answer in Copepoda:
    Can anybody give a name to this copepoda Lernaeocera ?

    Hello, I found this parasite on freshwater Esox lucius. Is it possible to give it a name ? 

    + 2 more attachments

    Jean François Cart

    Avez-vous une idée du nombre d'espèces, qui pourraient être confondues, présentes dans les eaux douces en France ?

    Il doit y avoir une espèce, envahissante Tracheliastes polycolpus que je n'ai pas encore observé, mais à part cela ? 


  • Agostino Prástaro added an answer in Foundations of Quantum Mechanics:
    How do we understand a conservation law (Noether's theorem) in quantum mechanics?

    In the classical mechanics Noether's theorem says that

    "if a system has a continuous symmetry property, then there are corresponding quantities whose values are conserved in time"

    As a simple particular case, a quantity A that doesn't depend on time explicitly, neither through other parameters on which it depends, i.e. dA/dt = 0, is a constant of motion.

    The question is what becomes of this law in quantum mechanics (QM)? Does it hold at all? And if it does, what is its meaning?

    The QM gives the following formula for the time derivative of an operator Ȃ:

    (1) dȂ/dt = ∂Ȃ/∂t + i/ħ (ĤȂ - ȂĤ),

    where Ĥ is the Hamiltonian of the system, and Ȃ is a Hermitic operator attached to an observable of the system.

    Assume now that Ȃ doesn't depend explicitly on time and commutes with Ĥ, therefore dȂ/dt = 0. How shall we understand this result? Does it mean that the value of the operator Ȃ is fixed during the system evolution, even if we don't measure it?

    Or, alternatively, does it mean that performing a measurement of Ȃ on identically prepared systems, we are bound to find the same value of Ȃ?

    In other words, in the QM, a quantity which is a constant of motion, possesses a value, and it is fixed in time, independently on whether we measure it or not? Or, alternatively, it takes a value only if we measure it, and the value is the same if we repeat the measurement on identically prepared systems?

    Agostino Prástaro

    Dear All,
    the full history about the question 'Does exist a quantum Noether's theorem ?' is more complex ...
    In fact, the answer depends on what mathematical model you have for the quantum system. Really it is well known that when one considers quantum mechanical systems encoded by the quantization of classical mechanical systems, then the classical Noether's theorem can do not work, for presences of so-called quantum anomalies.
    On the other hand it is well known also the incompleteness of the classical quantum mechanics ...

    Let me also add that in my theory of quantum gravity, unifying Einstein's GR with QM, there is instead a new full quantum Noether's theorem-type that can be associated to symmetries properties of the quantum dynamical equation (say \hat E_k). Furthermore, one can generalize Noether's theorem, by identifying suitable quantum differential forms that result closed on the solutions of the quantum system. When one considers the corresponding observed dynamical equations, say \hat E _k[i], then one can talk also of the corresponding observed quantum conservation laws. Then for such observed conservation laws one can see the relation between proper time of the observer and time-independence. This is related to the nonlinear quantum propagator encoding a quantum process.
    Of course I cannot go in some details here, but interested readers can look to these my work:

    1) http://www.sciencedirect.com/science/article/pii/S1468121805001720.
    2) http://www.sciencedirect.com/science/article/pii/S0362546X08006068.
    3) http://www.sciencedirect.com/science/article/pii/S1468121812000491.

    Important applications in High Energy Physics can be found in the following papers:

    4) http://arxiv.org/abs/1205.2894.
    5) http://arxiv.org/abs/1206.4856.

    For the impatient reader, let me shortly resume that, for example, the invariance of the observed quantum super Yang-Mills PDEs, (say (YM)[i]), with respect to time translations, allows us to state existence of an observed quantum energy conservation law, encoded by a suitable quantum three-form, say \omega_H,  that is closed on the solutions of (YM)[i]. When one considers such a conservation law on a nonlinear quantum propagator, say V, such that \partial V= N_1\bigcup P\bigcup N_2, with \partial P=\partial N_1\bigcup\partial N_2, where N_1 and N_2 are two space-like 3-dimensional compact manifolds, one can happen that the quantum charge Q_1=<N_1, \omega_H>\not=Q_2=<N_2,\omega_H>. This can occur whether the manifold P is not smooth. Since in general solutions encoding quantum interactions are singular ones, it follows that, in general, the initial quantum system, namely N_1, has a quantum energy charge Q_1  that differs from Q_2.

    Of course the full story is more complex ... but I do not go on technicalities here.

    My best regards,


  • Sagar Modi asked a question in Simulink:
    Response of boost converter is changed when I convert compensator from continuous to discrete?

    The response of boost converter changes when I am trying to discretize simulink matlab model.I changed my compensator transfer function from s domain to z domain using c2d command.However after changing in z domain my response of boost converter becomes unstable.

    Thank you. 

  • Uzoma Darlington Chima asked a question in Forestry:
    Are there empirical evidences to prove that the rain forests are actually the lungs of the earth?

    I am a researcher with interest in environmental forestry. It is often said that 'the rain forests are the lungs of the earth'. I will like to know if there are empirical evidences to buttress that assertion.

  • Elaya Perumal Ulagalanthaperumal added an answer in Seagrass:
    Which is the reliable and authentic online source for the Australian algae and seagrass identification?

    I want to identify few sea algae and sea grasses for my research. I've checked online but various sources are sowing various description for the same species. Can you suggest me some credible sources? 

    Elaya Perumal Ulagalanthaperumal

    Dear Subas, 

       You can relay on the site suggested by Jackson  because that seaweed site is a good source and it is really a worth full online source to believe. they do have lot of monographs information over their..

     for identification of your organism up to genus level you can use website and other online sources but  species identification please use standard monographs and research articles. after identifying your organisms species name please try to read the original article i.e. where it has been described for the first time. please try to compare with the holotype herbarium/material.... 

    good luck...

  • Miles John Padgett added an answer in Entanglement:
    What role do entanglement photons play in quantum imaging (ghost imaging)?

    Is it only to provide the correlation between the image and the object? What is the difference between the correlation via entanglement and classical correlation?

    Miles John Padgett

    When considering ghost imaging ones needs to distinguish systems in which the correlations apply to the average over many photons or at the level of individual photon pairs.  In the many photon case  (perhaps when a beam splitter is used to create two copies of the same random intensity distribution) then most of the main results of ghost imaging can still be achieved -- see work of Gatti et al. and Boyd et al.

    However, beams splitters can't make copies of single photons.  A very convenient way of making two photons with the same position is parametric down-conversion.  Although such sources are entangled, for ghost imaging one only needs correlation in position (c.f. EPR type experiments when you need to be able to show both).  So one can do ghost imaging based upon position correlation alone and in this situation it is a use of entanglement NOT a prove of it.

    In relation to EPR one can also perform ghost imaging using the momentum anti-correlation between the photon pairs -- so in that sense switching between the two cases of position correlation and (from the same source) momentum anti-correlation one can demonstrate something corresponding to the EPR paradox. see 

    EPR-based ghost imaging using a single-photon-sensitive camera,

    R S Aspden, D S Tasca, R W Boyd, and M J Padgett,

    New J. Phys. 15, 073032 (2013)

  • Maqsood Iqbal added an answer in EOR:
    What is limitations of proxy model?

    What is the maximum number of parameters and levels to be incorporated in polynomial proxy models of EOR processes?

    Maqsood Iqbal

    This is mainly depending upon which EOR processes is under discussion.

  • Bartosz Rustecki added an answer in PTCA:
    Can high PEEP be a risk factor for LV clot embolisation?

    Recent anterior wall MI --> s/p primary PTCA to LAD.  TTE reveals LV non-organized clot.  Patient develops ARDS, gets ventilated on high PEEP, and a few days later MRI Brain reveals multiple cerebral infarcts with a hemorrhagic infarct also.  Could the high PEEP employed for ARDS management been one of the risk factors for LV clot embolisation?

    Bartosz Rustecki

    No. I described situation clots ad infarcts are unrelated with high PEEP. Severe state related with ARDS is a risk factor by itself.

  • Asif Latif added an answer in Wastewater Treatment Plant:
    What's the best range of SVI (Sludge Volume Index) for best performances of Activated sludge in Wastewater treatment plant?

    To use SVI (Sludge Volume Index) as indicator of best performances of Activated sludge process in  wastewater treatment plant (Nitrogen removal, phosphorus removal).

    Asif Latif

    The SVI depends on the amount of solids in sludge. It typically ranges between 100-200 ml/g. Any value coming under this range will exhibit a better WAS. 

  • Mohammad Alipour added an answer in Scenario Analysis:
    Can anyone suggest a decent quantitative approach for extrapolating future quantities from past data (for energy supply on a national level)?

    To use it as a scenario analysis. Methods other than energy systems.

    Mohammad Alipour

    Thank you dear Prof. Knaub. That is very helpful..

  • Izaz Rahman added an answer in Algorithms:
    Can anyone with creating constrained boundaries in PSO algorithm?

    Hi everyone, I am trying to implement a modified PSO algorithm to Dynamic Economic Load Dispatch Problem. Following is some important data:

    P_min = [10, 20, 30, 40, 50];

    P_max = [75, 125, 175, 250, 300]; 

    No_of_Units = 5

    No_of_Hours = 24

    Power_demand: [410 435 475 530 558 608 626 654 690 704 720 740 704 690 654 580 558 608 654 704 680 605 527 463]; % in MW 

    I need help to initialize population random within the P_min and P_max, for each hour and each unit. ?

    Izaz Rahman

    Dear Mai Eladany, The will be great, if you  could send me the code please. My email address is as follows:


  • Phil Geis added an answer in Actinobacillus pleuropneumoniae:
    Can biofilm formation make my growth curve look strange?

    I'm working with Actinobacillus pleuropneumoniae, one that really knows how to form biofilm. My log growth curve is looking good the first hours but is then stagnating or even getting reduced some. after about 2 hour stagnation it is growing again. Can biofilm formation play a role in this? I don't really know if I can "trust" the growth and expect it to handle antibiotic in an optimal way.

    Phil Geis

    Biofilm-associated cells are effectively more resistant to antimicrobial agents.  Are you claiming novelty in killing just the pelagic cell population?

  • Archana Iyer added an answer in Trypsin:
    How can I trypsinize sHela?

    I have two questions, I am trying to trypsinize my sHela with trypsin 2 ml for 5 minutes in the incubator, then after checking the percentage of detaching cells under the microscope, It is always low as 30% or less, so how to do a perfect trypsinization to get as much cells. Second question, If I am incubating several 10-cm culture plates, can I put them over each other, like 4 plates over each other, I am afraid they get suffocated

    thanks in advance

    Archana Iyer

    I agree with the other comments. 2 mls might be too much. I've gotten away with using just 0.5ml of trypsin. Pre-warming the Trypsin helps. I usually remove the media, do 1-2 washes with PBS, add the trypsin , try and swirl the the dish so the entire surface is covered. I usually keep it the incubator for a min, If everything doesn't come off, I usually tap the dish gently against the hood floor and everything usually comes off.

  • Ardalan Daryaei asked a question in Linear Mixed Models:
    How can i have an outpout for random effects in mixed model analysis using R?

    I want to report the amount of Xand for random effects in linear mixed model using R (package lme4). which command should I use?

    Thanks for your helps.

  • Songli Zhu added an answer in SDS:
    How do I do a western blot a large molecular weight protein?

    Recently, I am working on DNAPKcs phosphorylation,which is 450 kDa, I am struggling with detection in my WB(Western Blot).

    First, our model organism is frog, so the first problem is the specificity of antibody.

    I tried to use 5%,6% SDS gel, and add SDS in my transfer buffer. However, it seems not be working. Usually, there is no signal or a strong background that I cannot see any band.

    Does anyone have some suggestions?

    Songli Zhu

    Actually I mean is after not before. Sorry for that.

    Sometimes I can see bands on the membrane. 

  • Vladimirs Strazdins added an answer in Body Surface Area:
    Is it suitable to index renal and many other physiologic function for Body Surface Area ?

    The question bases on the wide criticism  by which measuring and estimating the body surface area (BSA) are questioned. Within  the many doubts, it  was emphasized  the inadequate methods to measure and to estimate the body surface, the frequent change of the weight, on which are based practically all the formulae stated to estimate the body surface, and the criteria followed for indexation according to the equation : variable N x 1,73/BSA, where the standardized measure of 1,73 square meters was the average body surface  in 1927 , a measure that increased very much during the past years, at present attaining 1,97 square meters, this inducing an underestimation of the measure function, being 1,73/1,97  = 0,878, that is to say a reduction of about 12 %.

    Vladimirs Strazdins

    Dear Giancarlo, thanks for bringing up this issue! As we well know, nothing is perfect, but in my mind BSA ir better that body weight alone and also better than BMI. All of them has shortages and limitations and are not applicable in some cases (e.g. amputees). Nevertheless, we need one universal standard and I have no idea, what may replace the BSA at the moment. Actually, while analyzing pediatric renal functions, I've found that BSA-based results are much more precise in comparison to standard pediatric weight-based ones. More important, pediatric BSA-based results are compatible with adult ones, e.g. normal diuresis values, etc.

    In short - BSA is not perfect, but I do not know anything better for now. Any ideas, what can substitute it in a futrue? And, surely, 1,73 vs 1,97 issue should be addressed by the renal community.

  • Prasanta Roy added an answer in PID Control:
    Which has better performance and speed: Hardware PID or a software-programmed PID ?

    Which is better in terms of performance and speed: (options 1, 2 or 3)

    1: A (commercially available) hardware auto-tune fuzzy-PID controller (for example, see the link 1 below) having thermocouple input and solid-state relay (SSR) output, or

    2. A PID controller programmed using softwares like LabVIEW or MATLAB/SIMULINK (link 2-4) and interfaced (by a Data-acquisition card) to thermocouples for temperature (input) and SSR for controller action (output). I want to have precise temperature control of a custom-made electrical furnace for example.

    3. For implementing complex "Ramp-soak" temperature profiles, I am thinking to *program* the above hardware PID controller through MODBUS RTU/ASCII (whatever it supports) on a PC (using LabVIEW). i.e. I can read PV (process variable) and write SV (set variable) into the controller. Rest all is same as case 1. 

    I have access to all options above (hardwares and licensed softwares).

    Please share your *practical* experiences.


    + 3 more attachments

    Prasanta Roy

    Comparison is difficult because it depends on the specific application. In case of realization of PID in Lab-view or MATLAB 'Derivative' part needs special care. Derivative samples should be slower that the Data-acquisition card. The controller generated output in case of PID in Lab-view or MATLAB needs to go the hardware through an S/H operation. Which may give signal spikes to actuator. Hence the control signal needs to be filtered by an analog low pass filter which are generally embedded with the Data-acquisition cards now-a-days. The filter will delay the signal. So if the system dynamics is faster like inverted pendulum or Magnetic levitation system,  it may create problem........Design issues do not matter much but the implementation issues will matter specific to application in options (1), (2), (3),