Machine learning and statistical physics modeling of tetracycline adsorption using activated carbon derived from Cynometra ramiflora fruit biomass.

The current investigation reports the usage of adaptive neuro-fuzzy inference system (ANFIS) and artificial neural network (ANN), the two recognized machine learning techniques in modelling tetracycline (TC) adsorption onto Cynometra ramiflora fruit biomass derived activated carbon (AC). Many characterization methods utilized, confirmed the porous structure of synthesized AC. ANN and ANFIS models utilized pH, dose, initial TC concentration, mixing speed, time duration, and temperature as input parameters, whereas TC removal percentage was designated as the output parameter. The optimized configuration for the ANN model was determined as 6-8-1, while the ANFIS model employed trimf input and linear output membership functions. The obtained results showed a strong correlation, indicated by high R2 values (ANNR2: 0.9939 & ANFISR2: 0.9906) and low RMSE values (ANNRMSE: 0.0393 & ANFISRMSE: 0.0503). Apart from traditional isotherms, the dataset was fitted to statistical physics models wherein, the double-layer with a single energy satisfactorily explained the physisorption mechanism of TC adsorption. The sorption energy was 21.06 kJ/mol, and the number of TC moieties bound per site (n) was found to be 0.42, conclusive of parallel binding of TC molecules to the adsorbent surface. The adsorption capacity at saturation (Qsat) was estimated to be 466.86 mg/g - appreciably more than previously reported values. These findings collectively demonstrate that the AC derived from C. ramiflora fruit holds great potential for efficient removal of TC from a given system, and machine learning approaches can effectively model the adsorption processes.

Deciphering the role of Saliva in COVID 19: A global cross-sectional study on the knowledge, awareness and perception among dentists.

OBJECTIVES: The global pandemic outbreak of the coronavirus has instilled the quest amongst researchers on the expedited need for the early detection of viral load. Saliva is a complex oral biological fluid which not only causes the disease transmission but can be an effective alternative sample for detection of SARS-CoV2. This provides an ideal opportunity for dentists to be the frontline healthcare professionals who can collect the salivary samples; however the awareness of this amongst dentists is uncertain. Hence the aim of this survey was to evaluate the knowledge, perception and awareness of the role of saliva in detecting the SARS-CoV2 among dentists worldwide. METHODS: The online questionnaire comprising of 19 questions was shared to 1100 dentists worldwide and a total of 720 responses was collected. The data was tabulated, statistically analysed using the non- parametric Kruskal-Wallis test (p < 0.05). Based on the principal component analysis, 4 components (knowledge about virus transmission, perception about SARS-CoV2 virus, awareness on the sample collection and knowledge about prevention of the virus) were obtained which was compared with the 3 independent variables (years of clinical experience, occupation and region). RESULTS: A statistically significant difference was observed in the awareness quotient amongst the dentists with 0-5 years and greater than 20 years of clinical experience. In terms of the occupation, a significant difference was noted when comparing the postgraduate students to practitioners knowledge about the virus transmission. A highly significant difference was seen on comparing academicians and postgraduate students and also between academicians and practitioners. No significant difference was evidenced amongst the different regions, however the mean score was in the range of 3-3.44. CONCLUSION: This survey highlights the deficiency in the knowledge, perception and awareness among dentists worldwide.

Transition from Linear to Circular Motion in Active Spherical-Cap Colloids.

Nonspherical self-propelling colloidal particles offer many possibilities for creating a variety of active motions. In this work, we report on the transition from linear to circular motion of active spherical-cap particles near a substrate. Self-propulsion is induced by self-diffusiophoresis by catalytic decomposition of hydrogen peroxide (H2O2) on one side of the particle. Asymmetric distribution of reaction products combined with the asymmetric shape of the particle gives rise to two types of motions depending upon the relative orientation of the particle with respect to the underlying substrate. At a low concentration of H2O2, linear active motion is observed, whereas increasing the H2O2 concentration leads to persistent circular motion. However, the speed of self-propulsion is nearly independent of the size of the particle. The study demonstrates the use of nonspherical particles to create linear and circular motion by varying the fuel concentration.

Structure-function studies of HNF1A (MODY3) gene mutations in South Indian patients with monogenic diabetes.

Maturity-onset diabetes of the young (MODY) is a genetically heterogeneous monogenic form of diabetes characterized by onset of diabetes below 25 years of age, autosomal dominant mode of inheritance and primary defect in insulin secretion. Mutations in the gene (HNF1A) encoding transcription factor hepatocyte nuclear factor 1A (HNF-1A) results in one of the most common forms of MODY (MODY3). HNF-1A is mainly enriched in pancreatic ß-cells and hepatocytes and important for organ development and normal pancreatic function. We here report on the functional interrogation of eight missense HNF1A mutations associated with MODY3 in South Indian subjects, and the contributing effect of common variant (S487N) within HNF1A. Of the eight mutations, three mutations (p.R171G, p.G245R and p.R263H), in particular, affected HNF-1A function in transfected HeLa cells by reducing both transcriptional activity and nuclear localization, possibly due to disruption of the integrity of the three dimensional structure. The common variant p.S487N contributed further to the loss-of-function of p.R271Q (p.R271Q+p.S487N double mutant), in vitro, on both activity and localization. Our data on the first functional study of HNF1A mutations in South India subjects confers that the defect of the HNF-1A mutant proteins are responsible for MODY3 diabetes in these patients.

SnxTi1-xO2 solid-solution-nanoparticle embedded mesoporous silica (SBA-15) hybrid as an engineered photocatalyst with enhanced activity.

Synthesis of hybrids of a porous host-material (with well-dispersed embedded nanoparticles inside the pore), wherein each nanoparticle has precisely controlled properties (size and composition) poses a generic challenge. To this end, a new strategy is proposed to form SnxTi1-xO2 solid-solution-nanoparticles inside the pores of sphere-like mesoporous silica (SBA-15), with different percentages of Sn in the nanoparticle (varying from 5 to 50 at%), for enhanced photocatalysis. X-ray diffraction confirms the formation of solid-solution nanoparticles in the porous silica hybrid, while the location of nanoparticles and elemental composition are identified using electron microscopy. The hybrid with 5 at% of Sn (Sn0.05Ti0.95O2-sphere-like SBA-15) shows the maximum photocatalytic activity for degradation of rhodamine-B dye (first order rate constant for degradation, k = 1.86 h(-1)), compared to both pure TiO2-sphere-like SBA-15 (k = 1.38 h(-1)) or pure SnO2-sphere-like SBA-15 (k = 0.14 h(-1)) or other hybrids in this series. XPS and PL spectra suggest the formation of more oxygen vacancies during the replacement of Ti(4+) with Sn(4+). Electrochemical studies reveal that there is a reduction of charge transfer resistance from 910 kΩ cm(-2) for TiO2-sphere-like SBA-15, to 332 kΩ cm(-2) for Sn0.05Ti0.95O2-sphere-like SBA-15. These results imply that the enhancement in photocatalytic performance is as a result of delay in recombination of charge carriers. Therefore, the approach followed in the present work to form solid-solution nanoparticles inside a porous host without causing pore blockage, would be a promising route towards increasing reaction rates in catalytic applications of hybrid materials.

Regulatory Oversight of Cell- and Tissue-Based Therapeutic Products and Gene Therapy Products in Singapore.

The regulatory environment for cell- and tissue-based therapeutic products and gene therapy products is rapidly evolving and drug regulatory agencies are working towards establishing a risk-based system in the regulatory framework. Similarly in Singapore, a risk-based tiered approach has been applied whereby clinical trials and product licence of high-risk cell- and tissue-based therapeutic products (substantially manipulated products, products intended for nonhomologous use or combined products) and gene therapy products are regulated as medicinal products under the Medicines Act. There is no legal definition for cell- and tissue-based therapeutic and gene therapy products. The current working definition for a cell- and tissue-based therapeutic product is an article containing or consisting of an autologous or allogeneic human cell or tissue that are used for or administered to, or intended to be used for or administered to, human beings for the diagnosis, treatment, or prevention of human diseases or conditions. Gene therapy products are included under the current biological medicinal product definition.

Improved electrochemical performance of SnO2-mesoporous carbon hybrid as a negative electrode for lithium ion battery applications.

To utilize the high specific capacity of SnO2 as an anode material in lithium-ion batteries, one has to overcome its poor cycling performance and rate capability, which result from large volume expansion (∼300%) of SnO2 during charging-discharging cycles. Hence, to accommodate the volume change during cycling, SnO2 nanoparticles of 6 nm diameter were synthesized specifically only on the outer surface of the mesopores, present within mesoporous carbon (CMK-5) particles, resulting in an effective buffering layer. To that end, the synthesis process first involves the formation of 3.5 nm SnO2 nanoparticles inside the mesopores of mesoporous silica (SBA-15), the latter being used as a template subsequently to obtain SnO2-CMK-5 hybrid particles. SnO2-CMK-5 exhibits superior rate capabilities, e.g. after 30 cycles, a specific discharge capacity of 598 mA h g(-1), at a current density of 178 mA g(-1). Electrochemical impedance spectroscopy reveals that the SnO2-CMK-5 electrode undergoes a significant reduction in solid-electrolyte interfacial and charge transfer resistances, with a simultaneous increase in the diffusion coefficient of lithium ions, all these in comparison to an electrode made of only SnO2 nanoparticles. This enhances the potential of using the SnO2-CMK-5 hybrid as a negative electrode, in terms of improved discharge capacity and cycling stability, compared to other electrodes, such as only SnO2 or only CMK-5.

Inhibition of the interaction between NS3 protease and HCV IRES with a small peptide: a novel therapeutic strategy.

Recently, we have demonstrated that the protease domain of NS3 alone can bind specifically to hepatitis C virus (HCV) internal ribosome entry site (IRES) near the initiator AUG, dislodges human La protein and inhibits translation in favor of viral RNA replication. Here, by using a computational approach, the contact points of the protease on the HCV IRES were putatively mapped. A 30-mer NS3 peptide was designed from the predicted RNA-binding region that retained RNA-binding ability and also inhibited IRES-mediated translation. This peptide was truncated to 15 mer and this also demonstrated ability to inhibit HCV RNA-directed translation as well as replication. More importantly, its activity was tested in an in vivo mouse model by encapsulating the peptide in Sendai virus virosomes followed by intravenous delivery. The study demonstrates for the first time that the HCV NS3-IRES RNA interaction can be selectively inhibited using a small peptide and reports a strategy to deliver the peptide into the liver.

2-(1H-Benzimidazol-2-yl)phenol.

The title mol-ecule, C13H10N2O, is essentially planar, the maximum deviation from the plane of the non-H atoms being 0.016 (2) Å. The imidazole ring makes a dihedral angle of 0.37 (13)° with the attached benzene ring. An intra-molecular O-H⋯N hydrogen bond generates an S(6) ring motif. In the crystal, mol-ecules are linked through N-H⋯O hydrogen bonds, forming chains propagating in [001]. The crystal packing also features four π-π stacking inter-actions involving the imidazole ring, fused benzene ring and attached benzene ring system [centroid-centroid distances = 3.6106 (17), 3.6108 (17), 3.6666 (17) and 3.6668 (17) Å].

9-(2,4-Di-fluoro-phen-yl)-3,3,6,6-tetra-methyl-3,4,5,6,7,9-hexa-hydro-2H-xanthene-1,8-dione.

In the title compound, C23H24F2O3, the central pyran ring has a flat-boat conformation, whereas the two fused cyclo-hexenone rings adopt envelope conformations, with the C atom bearing the dimethyl substituent being the flap atom in each case. The pyran ring mean plane and the di-fluoro-phenyl ring are almost normal to each other, making a dihedral angle of 87.55 (4)°. In the crystal, mol-ecules are linked by pairs of C-H⋯O hydrogen bonds, forming inversion dimers with an R 2 (2)(8) ring motif. The F atom at position 2 on the di-fluoro-phenyl ring is disordered over the 2- and 6-positions, and has a refined occupancy ratio of 0.932 (3):0.068 (3).

2-(4-Fluoro-phen-yl)-1-(3-meth-oxy-phen-yl)-4,5-dimethyl-1H-imidazole.

In the title compound, C18H17FN2O, the imidazole ring makes dihedral angles of 68.81 (6) and 25.20 (8)° with the meth-oxy-phenyl and fluoro-phenyl rings, respectively. The dihedral angle between the meth-oxy-phenyl and fluoro-phenyl ring is 71.89 (6)°. In the crystal, mol-ecules are linked into inversion dimers with an R 2 (2)(8) graph-set motif by pairs of weak C-H⋯F inter-actions.

2-(Naphthalen-1-yl)-1-phenyl-1H-benzimid-azole benzene hemisolvate.

In the title compound, C23H16N2·0.5C6H6, the benzimidazole unit [maximum deviation = 0.0258 (6) Å] and the naphthalene ring system [maximum deviation = 0.0254 (6) Å] are both essentially planar and make a dihedral angle of 61.955 (17)°. The imidazole ring makes dihedral angle of 61.73 (4)° with the phenyl ring. An intra-molecular C-H⋯N hydrogen bond generates an S(6) ring motif. In the crystal, seven weak C-H⋯π inter-actions involving the fused ring system, the benzene solvent mol-ecule, the imidazole phenyl rings are observed, leading to a three-dimensional architecture.

Crystal structure of [4-(2-meth-oxy-phen-yl)-3-methyl-1-phenyl-6-tri-fluoro-methyl-1H-pyrazolo-[3,4-b]pyridin-5-yl](thio-phen-2-yl)methanone.

The title compound, C26H18F3N3O2S, a 2-meth-oxy-substituted derivative, is closely related to its 4-methyl- and 4-chloro-substituted analogues and yet displays no structural relationships with them. The thio-phene ring is disorder free and the -CF3 group exhibits disorder, respectively, in contrast and similar to that observed in the 4-methyl- and 4-chloro-substituted derivatives. The torsion angle which defines the twist of the thio-phene ring is -69.6 (2)° (gauche) in the title compound, whereas it is anti-clinal in the 4-methyl- and 4-chloro-substituted derivatives, with respective values of 99.9 (2) and 99.3 (2)°. The absence of disorder in the thio-phene ring facilitates one of its ring C atoms to participate in the lone inter-molecular C-H⋯O hydrogen bond present in the crystal, leading to a characteristic C(5) chain graph-set motif linking mol-ecules related through glides along [010]. An intra-moleculr C-H⋯N hydrogen bond also occurs.

Crystal structure of 4-sulfamoylanilinium di-hydrogen phosphate.

In the crystal structure of the title mol-ecular salt, C6H9N2O2S(+)·H2PO4 (-), the sulfomylalinium cations and the di-hydrogen phosphate anions form independent [100] chains through Ns-H⋯O (s = sulfamo-yl) and O-H⋯O hydrogen bonds, respectively. The chains are cross-linked by Na-H⋯O (a = amine) hydrogen bonds, generating (010) sheets. Two C-H⋯O hydrogen bonds involving diametrically opposite C atoms in the benzene ring of the cation as donors form chains parallel to [202] in which P=O and P-OH groups are acceptors. Together, these inter-actions lead to a three-dimensional network.

Identification of specific DNA binding residues in the TCP family of transcription factors in Arabidopsis.

The TCP transcription factors control multiple developmental traits in diverse plant species. Members of this family share an approximately 60-residue-long TCP domain that binds to DNA. The TCP domain is predicted to form a basic helix-loop-helix (bHLH) structure but shares little sequence similarity with canonical bHLH domain. This classifies the TCP domain as a novel class of DNA binding domain specific to the plant kingdom. Little is known about how the TCP domain interacts with its target DNA. We report biochemical characterization and DNA binding properties of a TCP member in Arabidopsis thaliana, TCP4. We have shown that the 58-residue domain of TCP4 is essential and sufficient for binding to DNA and possesses DNA binding parameters comparable to canonical bHLH proteins. Using a yeast-based random mutagenesis screen and site-directed mutants, we identified the residues important for DNA binding and dimer formation. Mutants defective in binding and dimerization failed to rescue the phenotype of an Arabidopsis line lacking the endogenous TCP4 activity. By combining structure prediction, functional characterization of the mutants, and molecular modeling, we suggest a possible DNA binding mechanism for this class of transcription factors.

Isomorphous methyl- and chloro-substituted small heterocyclic analogues obeying the chlorine-methyl (Cl-Me) exchange rule.

The two new isomorphous structures [3-methyl-4-(4-methylphenyl)-1-phenyl-6-trifluoromethyl-1H-pyrazolo[3,4-b]pyridin-5-yl](thiophen-2-yl)methanone, C26H18F3N3OS, (I), and [4-(4-chlorophenyl)-3-methyl-1-phenyl-6-trifluoromethyl-1H-pyrazolo[3,4-b]pyridin-5-yl](thiophen-2-yl)methanone, C25H15ClF3N3OS, (II), are shown to obey the chlorine-methyl exchange rule. Both structures show extensive disorder, treatment of which greatly improves the quality of the description of the structures. In addition, it is worth noting that the presence of extensive disorder may make it difficult to detect the isomorphism automatically during data-mining procedures (such as searches of the Cambridge Structural Database).

Supramolecular architectures of N-acetyl-L-proline monohydrate and N-benzyl-L-proline.

The title compounds, N-acetyl-L-proline monohydrate, C7H11NO3·H2O, (I), and N-benzyl-L-proline, C12H15NO2, (II), crystallize in the monoclinic space group P21 with Z' = 1 and Z' = 2, respectively. The conformation of C(γ) with respect to the carboxylic acid group in (I) is C(γ)-exo or UP pucker, with the pyrrolidine ring twisted, while in (II), it is C(γ)-endo or DOWN, with the pyrrolidine ring assuming an envelope conformation. The crystal packing interactions in (I) are composed of two substructures, one characterized by an R6(6)(24) motif through O-H...O hydrogen bonds and the other by an R4(4)(23) ring through C-H...O interactions. In (II), the crystal packing interactions consist of N-H...O and C-H...O hydrogen bonds. Proline (Pro) exists in its neutral form in (I) and is zwitterionic in (II). This difference in the ionization states of Pro is manifested through the absence of N-H...O and presence of O-H...O interactions in (I), and the presence of N-H...O and absence of O-H...O hydrogen bonds in (II). While C-H...O interactions are present in both (I) and (II), the geometry of the synthons formed by them and their mode of participation in intermolecular interactions is different. Though the title compounds differ significantly in terms of modifications in the Pro skeleton, the differences in their supramolecular structures may also be viewed as a result of the molecular recognition facilitated by the presence of a solvent water molecule in (I) and the zwitterionic state of the amino acid in (II).

4-Cyano-N-ethyl-spiro-[chromene-2,4'-piperidine]-1'-carboxamide.

The title compound, C17H19N3O2, crystallizes with two independent mol-ecules (A and B) in the asymmetric unit. In both mol-ecules, the pyran ring has a twisted conformation ((5)S4), with Q = 0.301 (3) Å, θ = 116.7 (6) and ϕ= 213.6 (7)° for mol-ecule A, and Q = 0.364 (2) Å, θ = 113.7 (3) and ϕ = 213.0 (4)° for mol-ecule B. In mol-ecule B, the terminal ethyl group is disordered over two orientations with an occupancy ratio of 0.55 (1):0.45 (1). In the crystal, mol-ecules A and B form very similar but separate R1(2)(7) motifs through N-H⋯O and C-H⋯O hydrogen bonds. The resulting chains along [001] are inter-linked by weaker C-H⋯O and C-H⋯π inter-actions, forming layers parallel to the bc plane.

1-(3-Meth-oxy-phen-yl)-4,5-dimethyl-2-phenyl-1H-imidazole.

In the title compound, C18H18N2O, the imidazole ring makes dihedral angles of 68.26 (7) and 22.45 (9)° with the meth-oxy-phenyl and phenyl rings, respectively. The dihedral angle between the meth-oxy-phenyl and phenyl ring is 71.86 (7)°. In the crystal, weak inter-molecular C-H⋯O and C-H⋯N hydrogen bonds link the mol-ecules into columns propagated in [101].

N-tert-But-oxy-carbonyl-α-(2-fluoro-benzyl)-l-proline.

In the title compound, C17H22FNO4, the pyrrolidine ring adopts an envelope conformation with the disordered com-ponents of the methylene C atom, with site occupancies of 0.896 (7) and 0.104 (7), being the flap on either side of the mean plane involving the other atoms of the ring. The carb-oxy-lic acid group forms dihedral angles of 72.06 (11) and 45.44 (5)° with the N-tert-but-oxy-carbonyl group and the 2-fluoro-benzyl group, respectively. In the crystal, two-dimensional layers of mol-ecules parallel to (001) are built through an R 4 (4)(23) motif generated via O-H⋯O, C-H⋯O and C-H⋯F inter-actions, and an R 2 (2)(11) motif generated by C-H⋯O and C-H⋯F inter-actions.