- Gorakhpur India
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Coumarin glycosides have shown immense potential for diverse biological activities and have been explored extensively as<br> highly prospective biomolecules. In recent years, coumarin glycosides have been used as enzyme inhibitor... more
Coumarin glycosides have shown immense potential for diverse biological activities and have been explored extensively as<br> highly prospective biomolecules. In recent years, coumarin glycosides have been used as enzyme inhibitor molecules, environmentally-<br> sensitive fluorescent sensors, the building material of single-excitation and dual emission graphene composite,<br> fluorophore-tagged glycosides, molecule to assay enzyme activity on model bacterial strains, the nucleoside monomer unit<br> for the photoswitchable formation of a DNA interstrand cross-link along with many other applications. In this review, we have<br> compiled biochemically afforded coumarin glycosides obtained via mutagenic synthesis, chemo-enzymatic synthesis and hairy<br> root culture system synthesis. This review will play the role of a reservoir of biochemically synthesized glycosylated coumarins<br> and encourage medicinal chemists to explore the potential of th...
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A wound is any physical injury involving a break in the skin, and exposed subcutaneous tissues provide a favorable substratum for a wide variety of microorganisms to contaminate and colonize. In this study a total of 870 plus samples were... more
A wound is any physical injury involving a break in the skin, and exposed subcutaneous tissues provide a favorable substratum for a wide variety of microorganisms to contaminate and colonize. In this study a total of 870 plus samples were collected from patients visiting B & B hospital suspecting wound infection and then analyzed. The causative agents were isolated, identified by culture and biochemical tests and their susceptibility pattern to antibiotics were determined by using CLSI guidelines. Out of total samples, 476(44.8%) showed bacterial growth. Among growth cases 22.9% were mixed growths. Among all bacterial isolates, 12 species were identified of them, 70.6% were Gram-negative and 29.4% were Gram-positive. Among Gram-positive isolates, Staphylococcus. Aureus (74.2%) was most common followed by CoNS (8.6%), Non hemolytic Streptococci (8.6%), Enterococcus spp. (4.3%) and â -haemolytic Streptococci (4.3%). Among Gram-negative bacteria, the most common isolate was Pseudomonas...
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Aspergillus fumigatus is an important pathogen of immunocompromised hosts, causing pneumonia and invasive disseminated disease with high mortality. To be able to analyze the expression of putative virulence-associated genes of A.... more
Aspergillus fumigatus is an important pathogen of immunocompromised hosts, causing pneumonia and invasive disseminated disease with high mortality. To be able to analyze the expression of putative virulence-associated genes of A. fumigatus , the use of the enhanced green fluorescent protein (EGFP) as a reporter was established. Two 5′ sequences, containing the putative promoters of the pyrG gene, encoding orotidine-5′-phosphate decarboxylase, and the pksP gene, encoding a polyketide synthase involved in both pigment biosynthesis and virulence of A. fumigatus , were fused with the egfp gene. The P pksP - egfp construct was integrated via homologous recombination into the genomic pksP locus. EGFP production was analyzed by fluorescence spectrometry, Western blot analysis, and fluorescence microscopy. Differential gene expression in A. fumigatus was observed. Fluorescence derived from the PYRG-EGFP fusion protein was detected during all developmental stages of the fungus, i.e., during ...
Research Interests: Microbiology, Biology, Medicine, Gene expression, Biological Sciences, and 10 moreInfection and immunity, Virulence, Green Fluorescent Protein, Aspergillus fumigatus, Multienzyme complexes, Amino Acid Sequence, Base Sequence, Differential expression, Molecular Sequence Data, and Medical and Health Sciences
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detected.[21 Thus, the fascinating 43-peptide antibiotic mi- crocin B17, which inhibits DNA-gyrase, contains four oxazole and four thiazole rings,[3b1 which arise by cyclizations and dehy- drogenations from di- and tripeptide units... more
detected.[21 Thus, the fascinating 43-peptide antibiotic mi- crocin B17, which inhibits DNA-gyrase, contains four oxazole and four thiazole rings,[3b1 which arise by cyclizations and dehy- drogenations from di- and tripeptide units containing Gly, Ser, and Cys residues of the precursor protein (69 residues) followed by cleavage of a leader peptide (26 residues). A wide variety of oxazole-, thiazole-, and thiazoline-containing natural products has also been isolated from marine organismst4"-'] and mi- croorganisms.~4~-m1 The reported syntheses of oxa~ole[~~
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The aim of the present study was to evaluate the in vitro cytotoxic activity of methanolic and aqueous extract of aerial parts of Cocculus hirsutus on MCF-7 breast cell lines. Qualitative phytochemical screening tests were performed to... more
The aim of the present study was to evaluate the in vitro cytotoxic activity of methanolic and aqueous extract of aerial parts of Cocculus hirsutus on MCF-7 breast cell lines. Qualitative phytochemical screening tests were performed to detect phytochemicals in the extracts. Antioxidant activity of the plant extracts were characterized by using DPPH free radical scavenging method. The cytotoxic activity of the extracts of Cocculus hirsutus on MCF-7 cells was investigated in vitro through MTT assay. The results showed Antioxidant activity using DPPH were found to be increased in a concentration dependent manner and decreased cell viability and cell growth inhibition in a dose dependent manner. The findings from this study indicated that methanolic and aqueous extracts of Cocculus hirsutus leaf possessed vast potential as a medicinal drug especially in breast cancer treatment.
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Triphenyl Sn(IV)-A(lII)-µ-oxoisopropoxide derivatives having different (NOONO and OONO) backbones were obtained by the reaction of triphenyltin acetate and aluminium isopropoxide with corresponding ligand. Through manipulation of reaction... more
Triphenyl Sn(IV)-A(lII)-µ-oxoisopropoxide derivatives having different (NOONO and OONO) backbones were obtained by the reaction of triphenyltin acetate and aluminium isopropoxide with corresponding ligand. Through manipulation of reaction stoichiometry, varieties of coordination compounds featuring µ-bridging coordination were obtained. 119 Sn NMR spectra of Ph 3 SnOAl(OPr i )L and Ph 3 SnOAl(L) 2 exhibit a single resonance, in solution, which is a characteristic of four-coordinated triphenyl complex. There are quite close structural and architectural similarities between both series of complexes. Physicochemical analysis confirmed the formation of Ph 3 SnOAl(OPr i )L and Ph 3 SnOAl(L) 2 derivatives. Both the derivatives of triphenyl Sn(IV)-Al(III)-µ-oxoisopropoxide showed tetra- and penta- coordination of metal centres with distorted tetrahedral and distorted trigonal-bipyramidal geometries for Sn(IV) and Al(III) respectively. These central metal ions are capable of organizing surr...
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A new isatin‐triazole tethered rhodamine based fluorescent probe R1 (1‐(2’’‐(4’‐(((3’’’,6’’’‐bis(diethylamino)‐3’’‐oxospiro[isoindoline‐1’’,9’’’‐xanthen]‐2’’‐yl)amino)methyl)‐1H‐1’,2’,3’‐triazolyl)ethyl)indoline‐2,3‐dione) has been... more
A new isatin‐triazole tethered rhodamine based fluorescent probe R1 (1‐(2’’‐(4’‐(((3’’’,6’’’‐bis(diethylamino)‐3’’‐oxospiro[isoindoline‐1’’,9’’’‐xanthen]‐2’’‐yl)amino)methyl)‐1H‐1’,2’,3’‐triazolyl)ethyl)indoline‐2,3‐dione) has been synthesized using click chemistry approach. Probe R1 exhibits a dual sensor property for Cu2+ and Fe3+ ions through turn‐on fluorescence response. A prominent colour change from colourless to pink allows the naked eye identification of aforementioned metal ions. R1 forms a 1:2 complex with Cu2+ and Fe3+ ions with binding constants 8.0 × 108 and 2.93 × 107 M−2, respectively. The binding mode is scrutinised through various spectroscopic techniques which is further supported by theoretical calculations. The detection limit of R1 for Cu2+ and Fe3+ ions is found to be 12.2 nM and 0.33 μM, respectively. Further, R1 has been evaluated for its potential to detect Cu2+ ions in biological systems using fluorescence cell imaging studies.
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Cancer is a class of diseases that is characterized by the uncontrollable or unstoppable growth of abnormal cells with the potential to invade or spread to other normal body parts. According to WHO estimates, globally 10 million new... more
Cancer is a class of diseases that is characterized by the uncontrollable or unstoppable growth of abnormal cells with the potential to invade or spread to other normal body parts. According to WHO estimates, globally 10 million new cancer cases are diagnosed each year. Its 100% prevention becomes a major challenge for the scientific fraternity. Therefore, there is an urgent need to discover new drugs that could overcome the present issue. In order to meet the challenges, a library of 22 novel 1H‐1,2,3‐triazol‐4‐yl‐methyl tethered 3‐pyrrolyl isatin derivatives have been synthesized and well characterized by using different spectral techniques. The newly synthesized conjugates were screened for their anti‐proliferative activity against breast cancer MCF‐7 and MDA‐MB‐231, as well as human embryonic HEK 293 cell lines by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay. Cytotoxicity studies revealed that six of the compounds among entire series are three‐fold mo...
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ABSTRACT
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The synthesis of novel pyrazolylnucleosides 3a–e, 4a–e, 5a–e, and 6a–e are described. The structures of the regioisomers were elucidated by using extensive NMR studies. The pyrazolylnucleosides 5a–e and 6a–e were screened for anticancer... more
The synthesis of novel pyrazolylnucleosides 3a–e, 4a–e, 5a–e, and 6a–e are described. The structures of the regioisomers were elucidated by using extensive NMR studies. The pyrazolylnucleosides 5a–e and 6a–e were screened for anticancer activities on sixty human tumor cell lines. The compound 6e showed good activity against 39 cancer cell lines. In particular, it showed significant inhibition against the lung cancer cell line Hop-92 (GI50 9.3 µM) and breast cancer cell line HS 578T (GI50 3.0 µM).
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To study whether telmisartan, an angiotensin II (AII) receptor blocker (ARB), modulates endothelial inflammation and oxidative cell damage induced by AII-independent stimuli in cultured human umbilical vein endothelial cell (HUVEC)s.... more
To study whether telmisartan, an angiotensin II (AII) receptor blocker (ARB), modulates endothelial inflammation and oxidative cell damage induced by AII-independent stimuli in cultured human umbilical vein endothelial cell (HUVEC)s. Endothelial inflammation, as reflected by increased VCAM-1 and ICAM-1 expression (ELISA), was induced by TNF-alpha, an inflammatory cytokine, and cell damage (COMET and MTT assay) by hydrogen peroxide, a reactive oxygen species. Losartan, another ARB, its active metabolites (EXP-3174, EXP-3179), dexamethasone, a synthetic steroid, and pyrrolidine dithiocarbamate (PDTC), an anti-oxidant, were the controls. The contribution of PPAR-gamma agonism was assessed through synthetic PPAR-gamma agonists and antagonists and the antagonism for AII-type 1 receptor-mediated stimuli by evaluating the interference against cell death induced by AII (MTT assay), a pro-apoptotic peptide that induces oxidative stress. The in vitro scavenging properties for oxyradicals were quantified by the TOSC assay. Telmisartan and PDTC reduced TNF-alpha-stimulated VCAM-1 in a concentration-dependent manner while losartan, EXP-3174, EXP-3179 and dexamethasone were ineffective. All compounds did not modify ICAM-1 expression. PPAR-gamma agonists or antagonists did not interfere with the effect of telmisartan. Both ARBs antagonized AII-induced cell death but only telmisartan reduced hydrogen peroxide-induced cell damage. Telmisartan scavenged selectively hydroxyl radicals without affecting peroxyl radicals and peroxynitrite. Telmisartan modulates pleiotropically TNF-alpha induced VCAM-1 expression and oxidative damage in vascular endothelium, possibly by acting as a hydroxyl radical scavenger. Those anti-inflammatory and antioxidant properties may contribute to the therapeutic effect, although the applicability of these data to the clinical situations has to be verified.
Research Interests: Pharmacology, Chemistry, Atherosclerosis, Oxidative Stress, Medicine, and 15 moreAntioxidants, Humans, Endothelial Cells, Vasculitis, Telmisartan, Clinical Sciences, Hydrogen Peroxide, Endothelial cell, Oxidative Damage, Benzimidazoles, Angiotensin II, Oxidants, Bio, Medical and Health Sciences, and Cardiovascular medicine and haematology
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Double-headed nucleoside monomers have immense applications for studying secondary nucleic acid structures. They are also well-known as antimicrobial agents. This review article accounts for the synthetic methodologies and the biological... more
Double-headed nucleoside monomers have immense applications for studying secondary nucleic acid structures. They are also well-known as antimicrobial agents. This review article accounts for the synthetic methodologies and the biological applications of double-headed nucleosides.
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Protein thresholds have been shown to act as an ancient timekeeping device, such as in the time to lysis of E. coli infected with bacteriophage lambda. The time taken for protein levels to reach a particular threshold for the first time... more
Protein thresholds have been shown to act as an ancient timekeeping device, such as in the time to lysis of E. coli infected with bacteriophage lambda. The time taken for protein levels to reach a particular threshold for the first time is defined as the first passage time of the protein synthesis system, which is a stochastic quantity. The first few moments of the distribution of first passage times were known earlier, but an analytical expression for the full distribution was not available. In this work, we derive an analytical expression for the first passage times for a long-lived protein. This expression allows us to calculate the full distribution not only for cases of no self-regulation, but also for both positive and negative self-regulation of the threshold protein. We show that the shape of the distribution matches previous experimental data on lambda-phage lysis time distributions. We also provide analytical expressions for the FPT distribution with non-zero degradation i...
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A new fluorescent sensor 5 having fused imidazopyridine scaffold has been synthesized via cascade cyclization. It exhibits highly sensitive and selective detection of Fe3+ (‘turn-on’) and Hg2+ (‘turn-off’) in vitro and in HeLa cells.
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Bio-catalytically synthesized sugar–PEG-based copolymers form stable micelles in an aqueous medium. These micelles from amphiphilic copolymer are able to efficiently solubilize and stabilize indocyanine green dye (ICG) under physiological... more
Bio-catalytically synthesized sugar–PEG-based copolymers form stable micelles in an aqueous medium. These micelles from amphiphilic copolymer are able to efficiently solubilize and stabilize indocyanine green dye (ICG) under physiological conditions.
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Enzymes, being remarkable catalysts, are capable of accepting a wide range of complex molecules as substrates and catalyze a variety of reactions with a high degree of chemo-, stereo- and regioselectivity in most of the reactions.... more
Enzymes, being remarkable catalysts, are capable of accepting a wide range of complex molecules as substrates and catalyze a variety of reactions with a high degree of chemo-, stereo- and regioselectivity in most of the reactions. Biocatalysis can be used in both simple and complex chemical transformations without the need for tedious protection and deprotection chemistry that is very common in traditional organic synthesis. This current review highlights the applicability of one class of biocatalysts viz.…
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Prompted from the diversity of the wider use and being an integral part of genetic material, an effort was made to synthesize pyrimidine pyrazole derivatives of pharmaceutical interest by oxidative cyclization of chalcones with... more
Prompted from the diversity of the wider use and being an integral part of genetic material, an effort was made to synthesize pyrimidine pyrazole derivatives of pharmaceutical interest by oxidative cyclization of chalcones with satisfactory yield and purity. A novel series of 1,3-dimethyl-6-hydroxy-2,4-dioxo-5-(1′-phenyl-3′-aryl-1H-pyrazol-5′-yl)-1,2,3,4-tetrahydropyrimidines (5a–d) and 1,3-diaryl-6-hydroxy-4-oxo-2-thioxo-5-(1′-phenyl-3′-aryl-1H-pyrazol-5′-yl)-1,2,3,4-tetrahydropyrimidines (5e–l) has been synthesized. The structures of these compounds were established on the basis of FT-IR, 1H NMR, 13C NMR, and mass spectral analysis. All the synthesized compounds were screened for their antimicrobial activity against bacteria and fungi. Among all the compounds, 5g was found to be the most active as its MIC was 31.25 µg/mL against S. aureus and B. cereus. The compounds 5h, 5c, and 5e also possess antibacterial activity with MIC values as 62.50, 125.00, and 500.00 µg/mL, respectively...
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A series of acylated coumarin derivatives have been evaluated for their in silico ADMET properties and in vitro antibacterial activities. In silico analysis confirmed their physicochemical properties in conformation with various layout... more
A series of acylated coumarin derivatives have been evaluated for their in silico ADMET properties and in vitro antibacterial activities. In silico analysis confirmed their physicochemical properties in conformation with various layout filters and further their ADMET properties were predicted. Antibacterial activities were evaluated by Resazurin based microbroth dilution assay against standard Gram positive bacteria: Staphylococcus aureus (MTCC No. 3160) and Bacillus cereus (MTCC No. 10085). When used alone, these derivatives showed higher MIC values. However, in combination with standard drugs they exhibited synergistic effects according to fractional inhibitory concentration index. The synergistic effect was further confirmed by time kill curves. Their cytotoxity was evaluated by haemolytic assay and they were found to be non-toxic upto a concentrations 500 µg ml-1. The data support the potential use of acylated coumarin derivatives as next generation adjuvants as evaluated by their in silico ADMET analysis and in vitro antibacterial and cytotoxicity evaluation. Further research involving these combinations is warranted. This study suggests that acylated coumarin derivatives act as antibacterial adjuvants in combination with standard drugs and have potential to be used in pharmaceutical preparations.
Research Interests: Chemistry, Medicine, In Vitro, Humans, Computer Simulation, and 15 moreAnimals, Gram Positive Bacteria, Antibacterial activity, Coumarins, Coumarin, Microbial Sensitivity Tests, Bacillus Cereus, Acylation, In Silico, Biochemistry and cell biology, Hemolysis, Resazurin, Chemical Phenomena, Drug synergism, and Minimum Inhibitory Concentration
We study the shape characteristics of osteosarcoma cancer cell lines on surfaces of differing hydrophobicity using Zernike moments to represent cell shape. We compare the shape characteristics of four invasive cell lines with a... more
We study the shape characteristics of osteosarcoma cancer cell lines on surfaces of differing hydrophobicity using Zernike moments to represent cell shape. We compare the shape characteristics of four invasive cell lines with a corresponding less-invasive parental line on three substrates. Cell shapes of each pair of cell lines are quite close and display overlapping characteristics. To quantitatively study shape changes in high-dimensional parameter space we project down to principal component space and define a vector that summarizes average shape differences. Using this vector we find that three of the four pairs of cell lines show similar changes in shape, while the fourth pair shows a very different pattern of changes. We find that shape differences are sufficient to enable a neural network to classify cells accurately as belonging to the highly invasive or the less invasive phenotype. The patterns of shape changes were also reproducible for repetitions of the experiment. We al...
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Correction for ‘Morphological signatures of actin organization in single cells accurately classify genetic perturbations using CNNs with transfer learning’ by Sydney Alderfer et al., Soft Matter, 2022, https://doi.org/10.1039/d2sm01000c.
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<p>(A). The time taken to reach 90% of maximum value for the protein undergoing a low-to-high transition as a function of the load. The system is de-dimensionalized as described in Supplementary <a... more
<p>(A). The time taken to reach 90% of maximum value for the protein undergoing a low-to-high transition as a function of the load. The system is de-dimensionalized as described in Supplementary <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003533#pcbi.1003533.s026" target="_blank">Text S1</a> section 1.1 and 3.2.1. (B). The time taken for the concentration of the protein undergoing a high-to-low transition to reach 10% of its maximum value. Note that the linear relationship for both-sided load transition times, and same-sided decay time, and opposite-sided rise time has a negative slope. The relationship for same-sided rise time and opposite sided decay time has a very small, but positive slope.</p
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Today I am going to share with you an interesting conversation between me and my cousin Apoorvi, who is a curious student of class 9. This conversation began after she saw me teaching Greatest Common Divisor to Priyanka. Priyanka lives in... more
Today I am going to share with you an interesting conversation between me and my cousin Apoorvi, who is a curious student of class 9. This conversation began after she saw me teaching Greatest Common Divisor to Priyanka. Priyanka lives in my neighborhood and she is a student of class four. Sometimes she visits my home for help in mathematics. One day after helping Priyanka with her homework, I started talking to Apoorvi
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<p>(A). The basic toggle switch is the network shown without the dotted line. Repressor 1 represses the production of Repressor 2 and vice versa. The dotted line denotes a positive feedback motif found in some natural circuits. (B).... more
<p>(A). The basic toggle switch is the network shown without the dotted line. Repressor 1 represses the production of Repressor 2 and vice versa. The dotted line denotes a positive feedback motif found in some natural circuits. (B). A cartoon of part of the MAPK activation pathway in T lymphocytes, adapted from <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003533#pcbi.1003533-Prasad2" target="_blank">[29]</a>, showing the role of Ras activation. Signals from peptide-MHC complexes are received at the TCR and lead to phosphorylation of the cytoplasmic chains of the TCR by the Src kinase, Lck. This recruits the kinase ZAP70 which trans-autoactivates and phosphorylates a scaffold called LAT, which recruits Grb2 and SOS to the plasma membrane. SOS activates Ras as as shown. (C) A simplified model of the Ras switch. RasGDP transforms into RasGTP via the enzyme SOS. However the catalytic rate of SOS increases when bound to RasGTP. This sets up an autocatalytic positive feedback. RasGTP is deactivated by enzymes called RasGAP's (among others).</p
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By the end of spring (May 31st), the COVID-19 death rate was remarkably unevenly distributed across the countries Europe. While the risk of COVID-19 mortality is known to increase with age, age-specific COVID-19 death rates across Europe... more
By the end of spring (May 31st), the COVID-19 death rate was remarkably unevenly distributed across the countries Europe. While the risk of COVID-19 mortality is known to increase with age, age-specific COVID-19 death rates across Europe were similarly aberrantly distributed, implying that differences in age structure is an unlikely source of European variation in COVID-19 mortality. To explain these mortality distributions, we present a simple model where more favorable survival environments promote longevity and the accumulation of health frailty among the elderly while less favorable survival environments induce a mortality selection process that results in lower health frailty. Because the age-related conditions of frailty render the elderly less resistant to SARS-CoV-2, pre-existing survival environments may be non-obviously positively related to the COVID-19 death rate. To quantify the survival environment parameter of our model, we collected historic cohort- and period-based ...
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Polyphenolics are secondary metabolites of plants and possess an array of biological activities (Amakura et al. 2008; Bracke et al. 2008; Naithani et al. 2008; Ghosh &amp;amp;amp;amp;amp;amp;amp; Scheepens 2009). The synthesis of a... more
Polyphenolics are secondary metabolites of plants and possess an array of biological activities (Amakura et al. 2008; Bracke et al. 2008; Naithani et al. 2008; Ghosh &amp;amp;amp;amp;amp;amp;amp; Scheepens 2009). The synthesis of a variety of natural polyphenolic compounds such as coumarins (Ghate et al. ...
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<p>The 3-dimensional plot is viewed with the xy-plane horizontal for better contrast. The x- and y-axes are numbers of molecules of R1 and R2 while the z-axis is either probabilities or the quasi-potential. (A). The probability... more
<p>The 3-dimensional plot is viewed with the xy-plane horizontal for better contrast. The x- and y-axes are numbers of molecules of R1 and R2 while the z-axis is either probabilities or the quasi-potential. (A). The probability distribution function (pdf) of the toggle switch of <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003533#pcbi-1003533-g005" target="_blank">Fig. 5</a> but now with a load of 20 molecules on Repressor 1 (R1). (B). The pdf of the toggle switch with a load of 20 molecules on R1 and 20 molecules on R2. (C). The quasi-potential of the toggle with a load of 20 molecules on R1, i.e. corresponding to panel A. (D). The quasi-potential of the toggle with equal loads of 20 molecules on each repressor, i.e. corresponding to panel B.</p
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<p>The 3-dimensional plot is viewed with the xy-plane horizontal for better contrast. The x- and y-axes are numbers of molecules of R1 and R2 while the z-axis is either probabilities or the quasi-potential. (A). The probability... more
<p>The 3-dimensional plot is viewed with the xy-plane horizontal for better contrast. The x- and y-axes are numbers of molecules of R1 and R2 while the z-axis is either probabilities or the quasi-potential. (A). The probability distribution function (pdf) of the toggle switch of <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003533#pcbi-1003533-g005" target="_blank">Fig. 5</a> but now with a load of 20 molecules on Repressor 1 (R1). (B). The pdf of the toggle switch with a load of 20 molecules on R1 and 20 molecules on R2. (C). The quasi-potential of the toggle with a load of 20 molecules on R1, i.e. corresponding to panel A. (D). The quasi-potential of the toggle with equal loads of 20 molecules on each repressor, i.e. corresponding to panel B.</p