Synthesis of diversely substituted quinazoline-2,4(1H,3H)-diones by cyclization of tert-butyl (2-cyanoaryl)carbamates.

The synthesis of diversely substituted quinazoline-2,4(1H,3H)-diones by cyclization of tert-butyl (2-cyanoaryl)carbamates using readily accessible Boc protected o-amino nitriles is reported. The reaction proceeds smoothly at room temperature using 1 equiv. of H2O2 under basic conditions. This reaction is compatible with a variety of aromatic/heteroaromatic substrates with different functional groups. This strategy can be utilized for the simplified synthesis of goshuyuamide II and an alkaloid isolated from Zanthoxylum arborescens in good yields. This method was also applied to the synthesis of quinazoline-2,4(1H,3H)-diones that are precursors of medicinally important compounds: alfuzosin, terazosin, prazosin, IAAP, doxazosin, FK 366 (zenarestat) and KF31327.

Organic Photoredox-Catalyzed S-Trifluoromethylation of Aromatic and Heteroaromatic Thiols.

A visible-light-mediated trifluoromethylation protocol was developed for the conversion of (hetero)aromatic thiols to their respective S-trifluoromethylated derivatives employing trifluoromethanesulfonyl chloride (CF3SO2Cl) as a cost-effective source of trifluoromethyl radical (CF3·) and a highly reducing organophotocatalyst, 3DPA2FBN. The developed methodology is operationally simple, providing access to a diverse range of products in up to 92% yield. A plausible mechanism has been postulated based on preliminary mechanistic studies, including irradiation on/off, UV-vis studies, and radical trapping experiments.

Fiber Optic Sensor Coated with Multiple Layers of Hexagonal Boron Nitride Nanosheets (BNNS) for the Detection of Volatile Organic Compounds.

Nowadays, volatile organic compound (VOC) detection is imperative to ensure environmental safety in industry and indoor environments, as well as to monitor human health in medical diagnosis. Gas sensors with the best sensor response, selectivity, and stability are in high demand. Simultaneously, the advancement of nanotechnology facilitates novel nanomaterial-based gas sensors with superior sensor characteristics and low power consumption. Recently, boron nitride, a 2D material, has emerged as an excellent candidate for gas sensing and demonstrated exceptional sensing characteristics for new-generation gas sensing devices. Herein, ultrathin porous boron nitride nanosheets (BNNSs) with large lateral sizes were synthesized using a facile synthesis approach, and their material characteristics were investigated utilizing a variety of analytical techniques, including X-ray diffraction, Fourier transform infrared spectroscopy, ultraviolet spectroscopy, X-ray photoelectron spectroscopy, and scanning electron microscopy. A BNNS-coated cladding-modified fiber optic sensor (FOS) probe was prepared and employed for VOC (ammonia, ethanol, and acetone) sensing across concentrations varying from 0 to 300 ppm. The BNNSs-coated FOS demonstrated better selectivity toward 300 ppm ammonia, and specifically annealed BNNSs displayed a maximum sensor response of 55% along with a response/recovery times of 15 s/34 s compared to its counterparts. The superior ammonia sensing performances could be attributed to the formation of ultrathin nanosheets and a porous surface with slit-like features in hexagonal boron nitride.

Secondary metabolite induced tolerance to Fusarium oxysporum f.sp. cubense TR4 in banana cv. Grand Naine through in vitro bio-immunization: a prospective research translation from induction to field tolerance.

An innovative tissue culture mediated incorporation of metabolite-based biomolecule (Bio-immune) at in vitro stage itself in banana cv. Grand Naine was developed and validated for the production of Fusarium oxysporum f.sp. cubense TR4 tolerant plantlets. The novel bio-immune formulation developed by us, exhibited a significant antifungal potency against Foc TR4 with a high percent inhibition (100%) at a 2.5% concentration of bio-immune on the 5th, 7th, and 9th DAI. Bio-immune integrated during in vitro shoot proliferation stage in banana cv. Grand Naine recorded significant enhancement in the growth of roots and shoots. Bio-immune (0.5%) fortified media produced 12.67 shoots per clump whereas control registered only 9.67 shoots per clump. Similarly, maximum root numbers (7.67) were observed in bio-immune plants which were significantly higher over control (5.0). The bio-immunized banana transplants recorded a higher survival rate (97.57%) during acclimatization as compared to the control (94.53%). Furthermore, evaluation of the bio-immunized plants in pot experiments revealed that unimmunized plants treated with FocTR4 (TF) exhibited mortality between 60 and 90 days. On the 90th day after planting, a high mean disease severity index (DSI) of 3.45 was observed with unimmunized plantlets while the bio-immunized plants (TFBI) and ICAR-FUSICONT treated plants (TFTR) showed substantially reduced DSI (0.20 and 1.00) compared to FocTR4 treated control (TF). Significant increases in polyphenol oxidase (PPO), peroxidase (POD), ß-1,3-glucanase, phenylalanine ammonia-lyase (PAL), chitinase activities, and enhanced phenol contents were recorded in bio-immunized plants compared to unimmunized plants. Field experiments at two different locations in Bihar, India revealed that bunch weight, no. of hands/bunch, and no. of fingers/hand of bio-immune treated plants were significantly higher compared to the control.

Antioxidant and angiotensin-I-converting enzyme (ACE-I) inhibitory activities of protein hydrolysates derived from water buffalo (Bubalus bubalis) liver.

In the current study, we attempted to use ginger as a novel and natural source of protease in comparison with other commercially available enzymes to extract and characterize antioxidant and antihypertensive hydrolysates from water buffalo liver, a protein rich offal. Hydrolysis of protein extracts from buffalo liver using proteinase-K, pronase-E and ginger protease significantly increased the %degree of hydrolysis (18.5-55%) and generated low-molecular weight peptides evident from SDS-PAGE. Enzyme treated hydrolysates exhibited higher (p < 0.05) DPPH radical scavenging activity (43.7-82.4%) and angiotensin-I-converting enzyme (ACE-I) inhibitory activity (46.9-50.1%) relative to control. Mass spectrometric analysis (MALDI-TOF MS) of selected gel-filtered fractions identified few important peptides derived from nuclear ribonucleoprotein, pyruvate kinase and phosphoglycerate kinase that possess strong antioxidant activity. Present findings indicate the efficacy of partially purified ginger as a novel source of protease in generating protein hydrolysates from water buffalo liver with significant antioxidant and antihypertensive activity in vitro. We successfully demonstrated the recovery of functional bioactive peptides from water buffalo liver which presents a potential opportunity for the meat industries to economically use this important byproduct.

Bacillus clausii UBBC-07 in the symptom management of upper respiratory tract infections in children: a double blind, placebo-controlled randomised study.

In children, upper respiratory tract infections (URTIs) are one of the most common causes of infections which often require outpatient consultations with the doctor. The purpose of this study was to evaluate the effect of probiotic Bacillus clausii UBBC-07 on symptom management of URTIs in children. In this double blind, randomised, placebo-controlled study, 90 children (age 4-7 years) with URTIs were equally divided into two groups, the probiotic and placebo. The children were instructed to take B. clausii UBBC-07 spores (2×109 per 5 ml vial) or placebo suspension daily twice for three months. The total duration of the study was 6 months, 3 months treatment and 3 months follow-up period. The parameters assessed were the mean number of URTIs, duration and severity of URTIs, absenteeism from school/childcare and immunity parameters, such as immunoglobulin (Ig)M, IgG, IgE and salivary IgA levels. At the end of treatment, there was a significant decrease in the number, duration and severity of URTIs in the probiotic treated group as compared to the baseline and placebo. IgE levels were significantly decreased and salivary IgA levels were significantly increased in the probiotic treated group suggesting probiotic mediated Th1/Th2 immune homeostasis to alleviate URTIs in children. In conclusion, B. clausii UBBC-07 may help in the reduction of symptoms of URTIs. The trial was registered prospectively with the Clinical Trial Registry of India (CTRI Reg. No: CTRI/2018/08/015282).

Boundaries of the Topologically Frustrated Dynamical State in Polymer Dynamics.

Using fluorescence microscopy and single-particle tracking, we have directly observed the dynamics of λ-DNA trapped inside poly(acrylamide-co-acrylate) hydrogels under an externally applied electric field. Congruent with the recent discovery of the nondiffusive topologically frustrated dynamical state (TFDS) that emerges at intermediate confinements between the traditional entropic barrier and reptation regimes, we observe the immobility of λ-DNA in the absence of an electric field. The electrophoretic mobility of the molecule is triggered upon application of an electric field with strength above a threshold value Ec. The existence of the threshold value to elicit mobility is attributed to a large entropic barrier, arising from many entropic traps acting simultaneously on a single molecule. Using the measured Ec which depends on the extent of confinement, we have determined the net entropic barrier of up to 130 kBT, which is responsible for the long-lived metastable TFDS. The net entropic barrier from multiple entropic traps is nonmonotonic with the extent of confinement and tends to vanish at the boundaries of the TFDS with the single-entropic barrier regime at lower confinements and the reptation regime at higher confinements. We present an estimate of the mesh size of the hydrogel that switches off the nondiffusive TFDS and releases chin diffusion in the heavily entangled state.

Needle insertion-induced quasiperiodic cone cracks in hydrogel.

Needle insertion, a standard process for various minimally invasive surgeries, results in tissue damage which sometimes leads to catastrophic outcomes. Opaqueness and inhomogeneity of the tissues make it difficult to observe the underlying damage mechanisms. In this paper, we use transparent and homogeneous polyacrylamide hydrogel as a tissue mimic to investigate the damages caused during needle insertion. The insertion force shows multiple events, characterised by a gradual increase in the force followed by a sharp fall. Synchronised recording of the needle displacement into the gel shows that each event corresponds to propagation of stable cone crack. Though sporadic uncontrolled cracking has been discussed earlier, this is the first report of nearly periodic, stable and well-controlled 3-D cone cracks inside the hydrogel during deep penetration. We show that the stress field around the needle tip is responsible for the symmetry and periodicity of the cone cracks. These results provide a better understanding of the fracture processes in soft and brittle materials and open a promising perspective in needle designs and the control of tissue damages during surgical operations.

Anomalous packing and dynamics of a polymer chain confined in a static porous environment.

Polymers in confined porous environments are ubiquitous throughout biology, physics, materials science, and engineering. Several experiments have suggested that in some porous environments, chain dynamics can become extremely slow. While phenomenological explanations exist, the exact mechanisms for these slow dynamics have not been fully characterized. In this work, we initiate a joint simulation-theory study to investigate chain packing and dynamics in a static porous environment. The main theoretical concept is the free energy of the chain partitioning into several chambers of the porous environment. Both the theoretical results and Langevin dynamics simulations show that chain packing in each of the chambers is predominantly independent of chain length; it is determined by the maximal packing of segments in each chamber. Dynamically, short chains (compared to the chamber size) become trapped in a single chamber and dynamics become extremely slow, characteristic of an Ogston sieving-like behavior. For longer chains, on the other hand, a hierarchy of slow dynamics is observed due to entropic trapping, characterized by sub-diffusive behavior and a temporary plateau in the mean square displacement. Due to the slow nature of the dynamics, the inevitable long-time diffusive behavior of the chains is not captured by our simulations. Theoretically, the slow dynamics are understood in terms of a free energy barrier required to thread the chain from one chamber to the next. There is overall qualitative and quantitative agreement between simulations and theory. This work provides foundations for a better understanding of how chain dynamics are affected by porous environments.

Single molecule electrophoresis of star polymers through nanopores: Simulations.

We study the translocation of charged star polymers through a solid-state nanopore using coarse-grained Langevin dynamics simulations, in the context of using nanopores as high-throughput devices to characterize polymers based on their architecture. The translocation is driven by an externally applied electric field. Our key observation is that translocation kinetics is highly sensitive to the functionality (number of arms) of the star polymer. The mean translocation time is found to vary non-monotonically with polymer functionality, exhibiting a critical value for which translocation is the fastest. The origin of this effect lies in the competition between the higher driving force inside the nanopore and inter-arm electrostatic repulsion in entering the pore, as the functionality is increased. Our simulations also show that the value of the critical functionality can be tuned by varying nanopore dimensions. Moreover, for narrow nanopores, star polymers above a threshold functionality do not translocate at all. These observations suggest the use of nanopores as a high-throughput low-cost analytical tool to characterize and separate star polymers.

Market potential and opportunities for commercialization of traditional meat products in North East Hill Region of India.

The North Eastern (NE) India is renowned for its preference for animal-based food. This region is known for its traditional meat products. However, the popularity of these products remains confined to the specific community/location. The knowledge on the traditional preparation methods is generally passed across generations through practice and word of mouth. The traditional style of preparation and the specific ingredients added to each product makes them unique. In this review, an attempt has been made to identify the initiatives, opportunities, and market potential for commercialization of the traditional meat products. These unique features and properties of the traditional meat products have been highlighted. The commercialization of these products will enhance entrepreneurship development and ensure quality ethnic products to the consumer in the NE hill region of India.

Molecular analysis of anthocyanin biosynthesis pathway genes and their differential expression in mango peel.

Mango fruit is cherished by masses for its taste and nutrition, contributed by color, flavor, and aroma. Among these, peel color is an important trait contributing to fruit quality and market value. We attempted to elucidate the role of key genes of the anthocyanin biosynthesis pathway related to fruit peel color from the leaf transcriptome of mango cultivar Amrapali. A total of 108 mined transcript sequences were assigned to the phenylpropanoid-flavonoid pathway from which 15 contigs representing anthocyanin biosynthesis genes were annotated. Alternate splice variants were identified by mapping against genes of Citrus clementina and Vitis vinifera (closest relatives) and protein subcellular localization was determined. Phylogenetic analysis of these pathway genes clustered them into distinct groups aligning with homologous genes of Magnifera indica, C. clementina, and V. vinifera. Expression profiling revealed higher relative fold expressions in mature fruit peel of red-colored varieties (Arunika, Ambika, and Tommy Atkins) in comparison with the green-peeled Amrapali. MiCHS, MiCHI, and MiF3H alternate splice variants revealed differential gene expression. Functionally divergent variants indicate availability of an allelic pool programmed to play critical roles in peel color. This study provides insight into the molecular genetic basis of peel color and offers scope for development of biomarkers in varietal improvement programs.

Not seeing the grass for the trees: Timber plantations and agriculture shrink tropical montane grassland by two-thirds over four decades in the Palani Hills, a Western Ghats Sky Island.

Tropical montane habitats, grasslands, in particular, merit urgent conservation attention owing to the disproportionate levels of endemic biodiversity they harbour, the ecosystem services they provide, and the fact that they are among the most threatened habitats globally. The Shola Sky Islands in the Western Ghats host a matrix of native forest-grassland matrix that has been planted over the last century, with exotic timber plantations. The popular discourse on the landscape change is that mainly forests have been lost to the timber plantations and recent court directives are to restore Shola forest trees. In this study, we examine spatiotemporal patterns of landscape change over the last 40 years in the Palani Hills, a significant part of the montane habitat in the Western Ghats. Using satellite imagery and field surveys, we find that 66% of native grasslands and 31% of native forests have been lost over the last 40 years. Grasslands have gone from being the dominant, most contiguous land cover to one of the rarest and most fragmented. They have been replaced by timber plantations and, to a lesser extent, expanding agriculture. We find that the spatial pattern of grassland loss to plantations differs from the loss to agriculture, likely driven by the invasion of plantation species into grasslands. We identify remnant grasslands that should be prioritised for conservation and make specific recommendations for conservation and restoration of grasslands in light of current management policy in the Palani Hills, which favours large-scale removal of plantations and emphasises the restoration of native forests.

Role of non-equilibrium conformations on driven polymer translocation.

One of the major theoretical methods in understanding polymer translocation through a nanopore is the Fokker-Planck formalism based on the assumption of quasi-equilibrium of polymer conformations. The criterion for applicability of the quasi-equilibrium approximation for polymer translocation is that the average translocation time per Kuhn segment, ⟨τ⟩/NK, is longer than the relaxation time τ0 of the polymer. Toward an understanding of conditions that would satisfy this criterion, we have performed coarse-grained three dimensional Langevin dynamics and multi-particle collision dynamics simulations. We have studied the role of initial conformations of a polyelectrolyte chain (which were artificially generated with a flow field) on the kinetics of its translocation across a nanopore under the action of an externally applied transmembrane voltage V (in the absence of the initial flow field). Stretched (out-of-equilibrium) polyelectrolyte chain conformations are deliberately and systematically generated and used as initial conformations in translocation simulations. Independent simulations are performed to study the relaxation behavior of these stretched chains, and a comparison is made between the relaxation time scale and the mean translocation time (⟨τ⟩). For such artificially stretched initial states, ⟨τ⟩/NK < τ0, demonstrating the inapplicability of the quasi-equilibrium approximation. Nevertheless, we observe a scaling of ⟨τ⟩ ∼ 1/V over the entire range of chain stretching studied, in agreement with the predictions of the Fokker-Planck model. On the other hand, for realistic situations where the initial artificially imposed flow field is absent, a comparison of experimental data reported in the literature with the theory of polyelectrolyte dynamics reveals that the Zimm relaxation time (τZimm) is shorter than the mean translocation time for several polymers including single stranded DNA (ssDNA), double stranded DNA (dsDNA), and synthetic polymers. Even when these data are rescaled assuming a constant effective velocity of translocation, it is found that for flexible (ssDNA and synthetic) polymers with NK Kuhn segments, the condition ⟨τ⟩/NK < τZimm is satisfied. We predict that for flexible polymers such as ssDNA, a crossover from quasi-equilibrium to non-equilibrium behavior would occur at NK ∼ O(1000).

Quantitative Assessment of Hand Dysfunction in Patients with Early Parkinson's Disease and Focal Hand Dystonia

OBJECTIVE: Motor impairments related to hand function are common symptoms in patients with movement disorders, such as Parkinson’s disease (PD) and focal hand dystonia (FHD). However, hand dysfunction has not been quantitatively assessed as a clinical tool for screening patient groups from healthy controls (HCs). The aim of our study was 1) to quantitatively assess hand dysfunction in patients with PD and FHD and its usefulness as a screening tool 2) to grade disease severity in PD and FHD based on hand dysfunction. METHODS: The current case-control study included HCs (n = 50) and patients with known history of PD (n = 25) or FHD (n = 16). Hand function was assessed by a precision grip task while participants lifted objects of 1.3 N and 1.7 N under dry skin conditions, followed by very wet skin conditions (VWSCs). Receiver operating characteristic and summative scoring analyses were performed. RESULTS: In PD, the combination of loading phase duration and lifting phase duration at quantitative cutoffs of 0.36 and 0.74 seconds identified 21/25 patients as diseased and 49/50 subjects as HCs with 1.7 N under VWSCs. In PD, 5/21 was graded as “mild” and 16/21 as “moderate cases.” In FHD, slip force at a cutoff of 1.2 N identified 13/16 patients as diseased and 41/50 subjects as HC with 1.7 N under VWSCs, but disease severity could not be graded. CONCLUSION: Our results demonstrate the use of precision grip task as an important clinical tool in assessment of hand dysfunction in movement disorder patients. Use of quantitative cutoffs may improve diagnostic accuracy and serve as a valuable adjunct to existing clinical assessment methods.

Adsorption and encapsulation of flexible polyelectrolytes in charged spherical vesicles.

We present a theory of adsorption of flexible polyelectrolytes on the interior and exterior surfaces of a charged vesicle in an electrolyte solution. The criteria for adsorption and the density profiles of the adsorbed polymer chain are derived in terms of various characteristics of the polymer, vesicle, and medium, such as the charge density and length of the polymer, charge density and size of the vesicle, electrolyte concentration and dielectric constant of the medium. For adsorption inside the vesicle, the competition between the loss of conformational entropy and gain in adsorption energy results in two kinds of encapsulated states, depending on the strength of the polymer-vesicle interaction. By considering also the adsorption from outside the vesicle, we derive the entropic and energy contributions to the free energy change to transfer an adsorbed chain in the interior to an adsorbed chain on the exterior. In this paper, we have used the Wentzel-Kramers-Brillouin (WKB) method to solve the equation for the probability distribution function of the chain. The present WKB results are compared with the previous results based on variational methods. The WKB and variational results are in good agreement for both the interior and exterior states of adsorption, except in the zero-salt limit for adsorption in the exterior region. The adsorption criteria and density profiles for both the interior and exterior states are presented in terms of various experimentally controllable variables. Calculation of the dependencies of free energy change to transfer an adsorbed chain from the interior to the exterior surface on salt concentration and vesicle radius shows that the free energy penalty to expel a chain from a vesicle is only of the order of thermal energy.

50th Anniversary Perspective: A Perspective on Polyelectrolyte Solutions.

From the beginning of life with the information-containing polymers until the present era of a plethora of water-based materials in health care industry and biotechnology, polyelectrolytes are ubiquitous with a broad range of structural and functional properties. The main attribute of polyelectrolyte solutions is that all molecules are strongly correlated both topologically and electrostatically in their neutralizing background of charged ions in highly polarizable solvent. These strong correlations and the necessary use of numerous variables in experiments on polyelectrolytes have presented immense challenges toward fundamental understanding of the various behaviors of charged polymeric systems. This Perspective presents the author's subjective summary of several conceptual advances and the remaining persistent challenges in the contexts of charge and size of polymers, structures in homogeneous solutions, thermodynamic instability and phase transitions, structural evolution with oppositely charged polymers, dynamics in polyelectrolyte solutions, kinetics of phase separation, mobility of charged macromolecules between compartments, and implications to biological systems.

Ratchet rectification effect on the translocation of a flexible polyelectrolyte chain.

We report a three dimensional Langevin dynamics simulation of a uniformly charged flexible polyelectrolyte chain, translocating through an asymmetric narrow channel with periodically varying cross sections under the influence of a periodic external electric field. When reflection symmetry of the channel is broken, a rectification effect is observed with a favored direction for the chain translocation. For a given volume of the channel unit and polymer length, the rectification occurs below a threshold frequency of the external periodic driving force. We have also observed that the extent of the rectification varies non-monotonically with increasing molecular weight and the strength of geometric asymmetry of the channel. Observed non-monotonicity of the rectification performance has been interpreted in terms of a competition between two effects arising from the channel asymmetry and change in conformational entropy. An analytical model is presented with predictions consistent with the simulation results.

Simulation of self-assembly of polyzwitterions into vesicles.

Using the Langevin dynamics method and a coarse-grained model, we have studied the formation of vesicles by hydrophobic polymers consisting of periodically placed zwitterion side groups in dilute salt-free aqueous solutions. The zwitterions, being permanent charge dipoles, provide long-range electrostatic correlations which are interfered by the conformational entropy of the polymer. Our simulations are geared towards gaining conceptual understanding in these correlated dipolar systems, where theoretical calculations are at present formidable. A competition between hydrophobic interactions and dipole-dipole interactions leads to a series of self-assembled structures. As the spacing d between the successive zwitterion side groups decreases, single chains undergo globule → disk → worm-like structures. We have calculated the Flory-Huggins χ parameter for these systems in terms of d and monitored the radius of gyration, hydrodynamic radius, spatial correlations among hydrophobic and dipole monomers, and dipole-dipole orientational correlation functions. During the subsequent stages of self-assembly, these structures lead to larger globules and vesicles as d is decreased up to a threshold value, below which no large scale morphology forms. The vesicles form via a polynucleation mechanism whereby disk-like structures form first, followed by their subsequent merger.

Communication: Theory of melt-memory in polymer crystallization.

Details of crystallization processes of a polymer at the crystallization temperature Tc from its melt kept initially at the melt temperature Tm depend profoundly on the nature of the initial melt state and often are accompanied by memory effects. This phenomenon is in contrast to small molecular systems where the supercooling (Tm (0)-Tc), with Tm (0) being the equilibrium melting temperature, and not (Tm - Tc), determines the nature of crystallization. In addressing this five-decade old puzzle of melt-memory in polymer crystallization, we present a theory to describe melt-memory effects, by invoking an intermediate inhomogeneous melt state in the pathway between the melt and crystalline states. Using newly introduced dissolution temperature T1 (0) for the inhomogeneous melt state and the transition temperature Tt (0) for the transition between the inhomogeneous melt and crystalline states, analytical formulas are derived for the nucleation rate as a function of the melt temperature. The theory is general to address different kinds of melt-memory effects depending on whether Tm is higher or lower than Tm (0). The derived results are in qualitative agreement with known experimental data, while making predictions for further experiments on melt-memory.