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Mitochondrial topisomerase 1 (Top1mt) is critical for mtDNA replication, transcription, and energy production. Here, we investigate the carrier-mediated targeted delivery of the anticancer drug irinotecan into the mitochondria to selectively trap Top1mt covalent complexes (Top1mtcc) and its role in anticancer therapeutics. We have designed a biocompatible mesoporous metal–organic framework (MOF) material, namely MIL-101(Fe), as the drug delivery carrier that selectively localizes inside mitochondria. In contrast to the traditional way of synthesising MOFs, here we have employed a vapour-assisted solvothermal method for the synthesis of MIL-101(Fe) using terephthalic acid as the organic linker and Fe(III) as the metal source. The advantage of this method is that it recycles the excess solvent (DMF) and reduces the amount of washing solvent. We demonstrate that MIL-101(Fe)-encapsulated irinotecan (MIL-Iri) was selectively targeted towards the mitochondria to poison Top1mtcc in a dose-dependent manner and was achieved at a low nanomolar drug concentration. We provide evidence that Top1mtcc generated by MIL-Iri leads to mtDNA damage in human colon and breast cancer cells and plays a significant role in cellular toxicity. Altogether, this study provides evidence for a new and effective strategy in anticancer chemotherapy. [ABSTRACT FROM AUTHOR]

In the study of parameterized streaming complexity on graph problems, the main goal is to design streaming algorithms for parameterized problems such that O (f (k) log O (1) n) space is enough, where f is an arbitrary computable function depending only on the parameter k. However, in the past few years very few positive results have been established. Most of the graph problems that do have streaming algorithms of the above nature are ones where localized checking is required, like Vertex Cover or Maximum Matching parameterized by the size k of the solution we are seeking. Chitnis et al. (SODA'16) have shown that many important parameterized problems that form the backbone of traditional parameterized complexity are known to require Ω (n) bits of storage for any streaming algorithm; e.g. Feedback Vertex Set, Even Cycle Transversal, Odd Cycle Transversal, Triangle Deletion or the more general F -Subgraph Deletion when parameterized by solution size k. Our contribution lies in overcoming the obstacles to efficient parameterized streaming algorithms in graph deletion problems by utilizing the power of parameterization. We focus on the vertex cover size K as the parameter for the parameterized graph deletion problems we consider. In this work, we consider the four most well-studied streaming models: the Ea, Dea, Va (vertex arrival) and Al (adjacency list) models. Surprisingly, the consideration of vertex cover size K in the different models leads to a classification of positive and negative results for problems like F -Subgraph Deletion and F -Minor Deletion. [ABSTRACT FROM AUTHOR]

Background: Fibular- and tibiofibular-based reconstructions are the gold standard treatment for posterolateral corner (PLC) injuries of the knee. Despite comparable outcomes in biomechanical studies, clinical results comparing these constructs remain elusive with no consensus reached regarding the best treatment option. Purpose: To perform a systematic review and meta-analysis to compare fibular- and tibiofibular-based techniques for posterolateral corner reconstruction. We aimed to identify whether any differences existed between the 2 techniques in terms of clinical outcomes and rotational and varus stability. Study Design: Meta-analysis; Level of evidence, 4. Methods: The Cochrane Controlled Register of Trials, PubMed, Medline, and Embase were used to perform a systematic review and meta-analysis using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) criteria with the following search terms ("posterolateral corner" OR "fibular collateral ligament" OR "lateral collateral ligament" OR "popliteus tendon" OR "popliteofibular ligament") AND ("reconstruction" OR "LaPrade" OR "Larson" OR "Arciero"). Data pertaining to all patient-reported outcome measures (PROMs), postoperative complications, and valgus and rotational stability were extracted from each study. The pooled outcome data were analyzed by random- and fixed-effects models. Results: After abstract and full-text screening, 6 clinical studies were included. In total, there were 183 patients, of which 90 received fibular-based and 93 tibiofibular-based reconstruction. The majority of studies used similar surgical techniques regarding tunnel orientation, attachment sites, and graft fixation sequence. There were no differences between the groups in terms of PROMs and subjective knee scores at a mean of 20.3 months. The techniques were equally effective in restoring varus and rotational stability. Subgroup analysis revealed that the stability of a posterior cruciate ligament reconstruction postoperatively was not affected by either construct. Conclusion: Both constructs had comparable clinical outcomes and were equally effective in restoring varus and rotational stability for PLC knee injuries. The fibular-based technique may offer advantages in view of being less technically demanding and invasive and requiring fewer grafts with a quicker operative time. However, higher quality studies are required to reinforce or refute such conclusions, as the majority of studies in this review were poor to fair quality. [ABSTRACT FROM AUTHOR]

In this paper, we focus on Hitting-Set , a fundamental problem in combinatorial optimization, through the lens of sublinear time algorithms. Given access to the hypergraph through a subset query oracle in the query model, we give sublinear time algorithms for Hitting-Set with almost tight parameterized query complexity. In parameterized query complexity , we estimate the number of queries to the oracle based on the parameter k , the size of the Hitting-Set. The subset query oracle we use in this paper is called Generalized d -partite Independent Set query oracle (GPIS) and it was introduced by Bishnu et al. (ISAAC'18). GPIS is a generalization to hypergraphs of the Bipartite Independent Set query oracle (BIS) introduced by Beame et al. (ITCS'18 and TALG'20) for estimating the number of edges in graphs. Since its introduction GPIS query oracle has been used for estimating the number of hyperedges independently by Dell et al. (SODA'20 and SICOMP'22) and Bhattacharya et al. (STACS'22), and for estimating the number of triangles in a graph by Bhattacharya et al. (ISAAC'19 and TOCS'21). Formally, GPIS is defined as follows: GPIS oracle for a d-uniform hypergraph H takes as input d pairwise disjoint non-empty subsets A 1 , ... , A d of vertices in H and answers whether there is a hyperedge in H that intersects each set A i , where i ∈ { 1 , 2 , ... , d }. For d = 2 , the GPIS oracle is nothing but BIS oracle. We show that d - Hitting-Set , the hitting set problem for d -uniform hypergraphs, can be solved using O ˜ d (k d log ⁡ n) GPIS queries. Additionally, we also showed that d - Decision-Hitting-Set , the decision version of d - Hitting-Set can be solved with O ˜ d (min ⁡ { k d log ⁡ n , k 2 d 2 }) GPIS queries. We complement these parameterized upper bounds with an almost matching parameterized lower bound that states that any algorithm that solves d - Decision-Hitting-Set requires Ω (( k + d d )) GPIS queries. [ABSTRACT FROM AUTHOR]

The aim of the study was to analyze the intracranial and spinal ependymomas with special reference to immunohistochemical markers in relation to short term prognosis. The present prospective study was conducted in the Department of Neurosurgery, Bangur Institute of Neurosciences and SSKM Hospital, IPGME and R, Kolkata from April 2020 to December 2021 in the Neurosurgery ward. 30 cases admitted in the department operated for suspected cases of intracranial and spinal ependymomas irrespective of any age groups and histologically confirmed thereafter by Pathology Department of SSKM hospital, IPGMER were included in the study. Age, sex, mode of presentation, clinical symptomatology, clinical findings, clinical, radiological investigations, surgical details, outcome data was recorded. The clinical follow-up observation was carried out by outpatient review. The patients were regularly followed up at 3, 6 and 12 months operation. Intracranial and spinal location was reported among 21 (70%) and 9 (30%) subjects respectively. During surgery, complete resection was achieved in 80% of the subjects. Out of 30 subjects, 90% of the subjects survived whereas mortality happened in 10% of the subjects. Most common complication was cranial nerve palsy (33.33%). The mean Ki-67 and p53 proliferative indices were significantly higher in grade III tumors as compared to grade II and grade I tumors. EMA was found to be positive in 70% of the subjects. The results concluded that p53 and Ki 67 indices when performed in routine diagnostic cases can supplement the histological diagnosis and at the same time these values could predict the relative difference in prognosis of various subtypes. [ABSTRACT FROM AUTHOR]

Background: Pediatric traumatic brain injury (TBI) is a global public health concern and is preventable, but there are no approved therapies to treat it definitely until date. Falls are the most frequent mode of injuries followed by road traffic accidents (RTA). Most of the TBIs have favorable outcome, though this is influenced by geographical, environmental, societal, and ethnic differences. Aims and Objectives: The aims of this study were to determine the several modes of injury, severity of injury, outcomes, and complications in the Eastern Indian population. Materials and Methods: Children-aged <18 years suffering from TBI who were attended to in Bangur Institute of Neurosciences, Institute of Post-Graduate Medical Education and Research, Kolkata, were prospectively studied for 1 year. Detailed history, clinical examinations, assessment of pupillary status, and Glasgow Coma Scale (GCS) score was recorded. Severity of TBI was done based on GCS score for each case. Computed tomography (CT) scan of head without contrast was the initial mode of neuro imaging and findings were recorded diligently. Patients were treated conservatively and surgically as required. Outcome was assessed in relation to age group, gender, initial GCS score, pupillary status, CT findings, intervention, and associated injuries. Simple statistical analysis was done. Results: Among the total 150 patients aged 1–18 years, most common mode of injury was fall in 56.66% followed by RTA in 23.33%, assault in 6.66%, and other modes such as sports, hit by object on head, and firearm injury in 13.33%. RTAs had a poor outcome in 14.29% and fall had a poor outcome in 14.12%. Poor outcome was associated with the highest (68%) being midline shift (MLS)>3 mm and it was 12.77% with MLS of <3 mm and it was 10.26% in patients with no MLS. It was noticed that chest, spinal, and multiple injuries were associated with poor outcome. Conclusion: The most important prognostic factors regarding pediatric TBI are GCS at presentation, pupillary status, associated injuries, and CT scan findings. [ABSTRACT FROM AUTHOR]

The goal of this work was to develop a reliable method to produce the well-validated microglial activation PET tracer, [18F]DPA-714, routinely for clinical and preclinical research using an IBA Synthera®. Optimization of literature methods included reduced precursor mass and use of TBA HCO 3 as the phase transfer agent in place of Kryptofix® 222 in a 65-min synthesis with an average activity yield of 24.6 ± 3.8% (n = 5). Successful quality control testing and process validation results are reported. • An IND-approved method for production of [18F]DPA-714 on an IBA Synthera® is reported. • Reduction of precursor mass and replacement of Kryptofix® 222 as phase transfer agent support production of tracer in reliable quantities for clinical research. • Justification of 5% injected ethanol in pediatric PET tracer preparations was outlined. [ABSTRACT FROM AUTHOR]

Chronobiologists and sleep researchers often need to estimate various rhythm and sleep parameters from locomotor activity data from different organisms. The available open-source or expensive paid tools do not offer consolidated analysis and visualization options in one bundle, are often cumbersome for users unfamiliar with coding, offer very low customization options, introduce sources of human errors by requiring users to manually pick period and power values from periodogram plots, and do not generate reproducible reports. We present VANESSA, a family of cross-platform apps written in R, which, in our opinion, have several advantages compared with available tools—(a) open-source; (b) automatic period-power detection; (c) time-series filtering and smoothing; (d) high-resolution publication-quality figures with dynamic coloring, resizing, and light/dark shading; (e) reproducible code-report generation; (f) analysis and visualization of multiple monitor files, defining genotypes and replicates separately; and (g) sleep profile analysis, various sleep parameter estimations, quantification, bout analysis, and latency analysis. The current version of the app is for data acquired through Drosophila Activity Monitors (DAM, TriKinetics) but can be easily extended to that from other data acquisition systems and from other organisms. We will continue to develop VANESSA with more useful features and version control will be done via archiving versions with significant changes on GitHub (https://github.com/orijitghosh/VANESSA-DAM) and Zenodo. [ABSTRACT FROM AUTHOR]

Topoisomerases regulate DNA topology, organization of the intracellular DNA, the transmission of genetic materials, and gene expressions. Other than the nuclear genome, mitochondria also harbor the small, circular DNA (mtDNA) that encodes a critical subset of proteins for the production of cellular ATP; however, mitochondria are solely dependent on the nucleus for all the mitochondrial proteins necessary for mtDNA replication, repair, and maintenance. Mitochondrial genome compiles topological stress from bidirectional transcription and replication, therefore imports four nuclear encoded topoisomerases (Top1mt, Top2α, Top2β, and Top3α) in the mitochondria to relax mtDNA supercoiling generated during these processes. Trapping of topoisomerase on DNA results in the formation of protein-linked DNA adducts (PDAs), which are widely exploited by topoisomerase-targeting anticancer drugs. Intriguingly mtDNA is potentially exposed to DNA damage that has been attributed to a variety of human diseases, including neurodegeneration, cancer, and premature aging. In this review, we focus on the role of different topoisomerases in the mitochondria and our current understanding of the mitochondrial DNA damage through trapped protein-DNA complexes, and the progress in the molecular mechanisms of the repair for trapped topoisomerase covalent complexes (Topcc). Finally, we have discussed how the pathological DNA lesions that cause mtDNA damage, trigger mitochondrial fission and mitophagy, which serve as quality control events for clearing damaged mtDNA. [ABSTRACT FROM AUTHOR]

The grid obstacle representation , or alternately, ℓ 1 -obstacle representation of a graph G = (V , E) is an injective function f : V → Z 2 and a set of point obstacles O on the grid points of Z 2 (where no vertex of V has been mapped) such that u v is an edge in G if and only if there exists a Manhattan path between f (u) and f (v) in Z 2 avoiding the obstacles of O and points in f (V). This work shows that planar graphs admit such a representation while there exist some non-planar graphs that do not admit such a representation. Moreover, we show that every graph admits a grid obstacle representation in Z 3. We also show NP-hardness result for the point set embeddability of an ℓ 1 -obstacle representation. [ABSTRACT FROM AUTHOR]

E-Rickshaw is an E-vehicle that has three wheels, a rechargeable battery driven electric motor as engine. E-rickshaw has become very popular due to low operating cost, low maintenance cost, eco-friendliness and ease of driving. It is perfect for small distance transport. As a last mile connector, it has transformed the public transport system in India. The low cost electric vehicle carries enough people to make a decent income and hence has become a source of livelihood for many. For considering the issues in this paper, detailed attributes of E-rickshaw are studied and Analytical Hierarchy Process (AHP) has been applied to calculate criteria weights for the sorted attributes. Subsequently, Technique for Order Preference by Similarity to Ideal Solution (TOPSIS), a Multi Criteria Decision Making (MCDM) technique has been applied for the selection of best E-Rickshaw. In this paper, sensitivity analysis and comparative analysis have been conducted for further insight. [ABSTRACT FROM AUTHOR]

We investigated the combined effect of chitosan (CHT) and putrescine (PUT) on the postharvest shelf life of Capsicum fruit concerning the metabolism of reactive oxygen species (ROS) through direct and indirect effects on ripening characters cell wall hydrolyzing enzyme and ROS metabolism. The PUT and CHT directly affected quality indices like color, firmness and water loss with a concomitant oxidative bust in the development of O 2 •− and H 2 O 2 in fruit pulp. This was accompanied by significant suppression of respiratory flux, a decrease of total soluble solids and ascorbic acid content throughout postharvest storage. PUT applied with CHT modified the oxidative metabolism of fruits by a significant reduction in the level of O 2 •− and H 2 O 2 content. In addition, a significant accumulation of total polyamine under respective treatment was reasonably correlated with both ROS producing enzyme as well as H 2 O 2 and O 2 •− . Wall hydrolyzing enzymes like pectin methyl esterase and cellulase had marked downregulation both under PUT and CHT + PUT treatment. Moreover, on close observation, the combinational effects of PUT and CHT had better effects in the regulation of those enzymes as compared to individual treatment. Fruits restore higher antioxidative capacities as evident with superoxide dismutase (SOD), guaiacol peroxidases (GPX), ascorbate peroxidase (APX) catalase (CAT), glutathione peroxidase (GPX), NADPH oxidase (NOX) and glutathione reductase (GR), indicating their roles on fruit coat softening. Finally, the treatment of PUT and CHT in combination increased shelf life vis-à-vis the quality of fruit. • Chitosan and putrescine enhance antioxidant defense system in chilli fruit. • Chitosan and putrescine improve the physiology and maintain the quality of chilli fruit. • Chitosan and putrescine regulate cell wall hydrolyzing enzymes. • Chitosan and putrescine are beneficial for increasing the shelf life of chilli fruits. [ABSTRACT FROM AUTHOR]

Heritable variation in the timing of rhythmic events with respect to daily time cues gives rise to chronotypes. Despite its importance, the mechanisms (clock or non-clock) regulating chronotypes remain elusive. Using artificial laboratory selection for divergent phasing of emergence of adults from pupae, our group has derived populations of Drosophila melanogaster which are early and late chronotypes for eclosion rhythm. Several circadian rhythm characteristics of these populations have since been described. We hypothesized that our selection protocol has inadvertently resulted in selection for masking, a non-clock phenomenon, in the early chronotype due to the placement of our selection window (which includes the lights-ON transition). We designed experiments to discriminate between enhanced masking to light versus circadian clock mediated changes in determining enhanced emergence in the morning window in our early chronotypes. Using a series of phase-shift protocols, LD-DD transition, and T -cycle experiments, we find that our early chronotypes have evolved positive masking, and their apparent entrained phases are largely contributed by masking. Through skeleton T -cycle experiments, we find that in addition to the evolution of greater masking, our early chronotypes have also evolved advanced phase of entrainment. Furthermore, our study systematically outlines experimental approaches to examine relative contributions of clock versus non-clock control of an entrained behavior. Although it has previously been suggested that masking may confer an adaptive advantage to organisms, here we provide experimental evidence for the evolution of masking as a means of phasing that can complement clock control of an entrained behavior. [ABSTRACT FROM AUTHOR]

Validated analytical methods must be used for accurate and precise determination of identity, purity, strength, and quality of any pharmaceutical dose intended for human administration. Consequently, all analytical methods must be validated per USP <1225> and the ICH Q2R1 guidelines to meet the cGMP requirements of the FDA and EMA. A reversed-phase high-performance liquid chromatography analytical method, with <10 min run time, was developed for the analysis of [11C]nicotine. The analytical method was found to be specific, accurate, suitable, robust, precise, and linear for [11C]nicotine, nicotine, and (±) nornicotine in the concentration ranges studied. The LOD and LOQ values were also established. [ABSTRACT FROM AUTHOR]

The article provide first-in-class evidence that shape-changing and self-latching microdevices enhance the efficacy of extended drug delivery. It mentions about the extended-release gastrointestinal (GI) luminal delivery substantially increases the ease of administration of drugs and consequently the adherence to therapeutic regimens.

• 5-Lipoxygenase regulates APP and other A-beta processing genes. • Cysteinyl leukotriene receptors are increased in models of Alzheimer's. • 5-Lipoxygenase and cysteinyl leukotriene receptor blockers alleviate Alzheimer's-related cognitive decline. • 5-Lipoxygenase and cysteinyl leukotriene receptor blockers alleviate Alzheimer's-related neuroinflammation. 5-lipoxygenase (ALOX5) is an enzyme involved in arachidonic acid (AA) metabolism, a metabolic pathway in which cysteinyl leukotrienes (CysLTs) are the resultant metabolites. Both ALOX5 and CysLTs are clinically significant in a number of inflammatory diseases, such as in asthma and allergic rhinitis, and drugs antagonizing the effect of these molecules have long been successfully used to counter these diseases. Interestingly, recent advances in 'neuroinflammation' research has led to the discovery of several novel inflammatory pathways regulating many cerebral pathologies, including the ALOX5 pathway. By means of pharmacological and genetic studies, both ALOX5 and CysLTs receptors have been shown to be involved in the pathogenesis of Alzheimer's disease (AD) and other neurodegenerative/neurological diseases, such as in Parkinson's disease, multiple sclerosis, and epilepsy. In both transgenic and sporadic models of AD, it has been shown that the levels of ALOX5/CysLTs are elevated, and that genetic/pharmacological interventions of these molecules can alleviate AD-related behavioral and pathological conditions. Clinical relevance of these molecules has also been found in AD brain samples. In this review, we aim to summarize such important findings on the role of ALOX5/CysLTs in AD pathophysiology, from both the cellular and the molecular aspects, and also discuss the potential of their blockers as possible therapeutic choices to curb AD-related conditions. [ABSTRACT FROM AUTHOR]

Circadian rhythms in adult eclosion of Drosophila are postulated to be regulated by a pair of coupled oscillators: one is the master clock that is light sensitive and temperature compensated and the other that is a slave oscillator whose period is temperature sensitive and whose phase is reflected in the overt behavior. Within this framework, we reasoned that in populations of Drosophila melanogaster that have been artificially selected for highly divergent phases of eclosion rhythm, there may be changes in this network of the master-slave oscillator system, via changes in the temperature-sensitive oscillator and/or the coupling of the light- and temperature-sensitive oscillators. We used light/dark cycles in conjunction with different constant ambient temperatures and 2 different amplitudes of temperature cycles in an overall cool or warm temperature and analyzed phases, gate width, and normalized amplitude of the rhythms in each of these conditions. We found that the populations selected for eclosion in the morning (early flies) do not vary their phases with change in temperature regimes, whereas the populations selected for eclosion in the evening (late flies) show phase lability of up to ~5 h. Our results imply a genetic correlation between timing of behavior and temperature sensitivity of the circadian clock. [ABSTRACT FROM AUTHOR]

Delaunay protection is a measure of how far is a Delaunay triangulation from being degenerate. In this short paper we study the protection properties and other quality measures of the Delaunay triangulations of a family of lattices that is obtained by distorting the integer grid in R d. We show that the quality measures of this family are maximized for a certain distortion parameter, and that for this parameter, the lattice is isometric to the permutahedral lattice , which is a well-known object in discrete geometry. [ABSTRACT FROM AUTHOR]

We report multifunctional properties of the charge disproportionate correlated electronic system La0.5Ba0.5FeO3 synthesized by conventional solid state reaction route. The bulk sample undergoes semiconductor-metal like transition at TSM = 102 K showing appreciable magnetoresistance (∼20%) around TSM even at a low field (∼0.5 T). A crossover of electrical conduction mechanism from Mott's variable range hopping to small polaron hopping occurs around 210 K, well above TSM. Analysis of the transport, magnetic susceptibility, and magnetization data in the light of de Gennes proposal indicates the formation of canted antiferromagnetic spin order preceded by charge ordering in La0.5Ba0.5FeO3. Nonsaturation behavior and nonlinearity of the M-H curve at low temperature and at high field (∼5 T), confirms the canted spin order. The observed resistive transition is considered to be associated with the onset of weak ferromagnetic ordering in the canted antiferromagnetic spin state of the materials. Moreover, novel ferroelectric like behavior showing electric field-polarization hysteresis loop below the charge ordering temperature along with anomalous magnetocapacitance response representing magnetoelectric coupling is also observed. In the low temperature regime spin lattice coupling might be responsible for exhibiting magnetocapacitance in La0.5Ba0.5FeO3. Such multifunctional character implies fundamental as well as technological importance of this sample. [ABSTRACT FROM AUTHOR]

Given a set system (X , R) such that every pair of sets in R have large symmetric difference, the Shallow Packing Lemma gives an upper bound on | R | as a function of the shallow-cell complexity of R . In this paper, we first present a matching lower bound. Then we give our main theorem, an application of the Shallow Packing Lemma: given a semialgebraic set system (X , R) with shallow-cell complexity φ (· , ·) and a parameter ϵ > 0 , there exists a collection, called an ϵ -Mnet, consisting of O (1 ϵ φ (O (1 ϵ) , O (1))) subsets of X, each of size Ω (ϵ | X |) , such that any R ∈ R with | R | ≥ ϵ | X | contains at least one set in this collection. We observe that as an immediate corollary an alternate proof of the optimal ϵ -net bound follows. [ABSTRACT FROM AUTHOR]

Background: Strong surgical repair is the mechanical basis of early mobilization and prerequisite for biological healing following tendon grafting. Side to side and pulvertaft repairs were developed to meets these demands. However, these techniques have later been modified to improve the strength of repair but their characteristics have not been compared. Methods: We compared biomechanical strength of the modified side-to-side (SS) repair with the modified Pulvertaft (PT) repair technique in turkey tendons keeping overlap length, anchor points, type of suture, suture throw and amount of suture similar. Two investigators performed 34 repairs during one summer month to test the tensile strength of the repair using mechanical strength testing machine. Variables measured were maximum load, load to first failure, modulus, load at break, mode of failure, site of failure, tensile strain, tensile stress. The statistical comparison was carried by Levene's test and T test for means. Results: The mean maximum load for modified SS repair was 50.3 (SD 13.7) N and modified PT repair was 46.9 (SD 16.4) N. The tensile stress at maximum load for SS and modified PT repair was 4.7 (SD 4) MPa and 4.2 (SD 3) MPa respectively. The suture cut through was the commonest mode of failure. Conclusions: We found no statistical difference between 2 repairs in load at which they started failing (p = 0.16), and maximum load repairs could withstand (p = 0.35). Our study uniquely compares two techniques under standard conditions, and contrary to existing evidence found no difference. However, in our opinion the number of anchor points may have a greater impact than number of weaves on the strength. [ABSTRACT FROM AUTHOR]

Scorpion venom components have multifaceted orientation against bacterial, viral, fungal infections and other neuronal disorders. They can modulate the ion channels (K+, Na+, Cl−, Ca2+) of our body and this concept has been hypothesized in formulating pharmaceuticals. The triumphant achievement of these venom components as formulated anticancer agent in Phase I and Phase II clinical trials allure researchers to excavate beneficial venom components prohibiting DNA replication in malignant tumor cells. This review brings forth the achievements of Science and Technology in classifying the venom components as therapeutics and further application in drug product development. [ABSTRACT FROM AUTHOR]

A novel, rapid, and automated loop method for the synthesis of [ 11 C]nicotine was developed and optimized. The method involves, a reaction of the precursor, ( + ) nornicotine or (-) nornicotine, with a gas-phase produced [ 11 C]CH 3 I in an 800 µL loop at 75 °C for 5 min followed by a semi-preparatory Reversed-Phase High-Performance Liquid Chromatography (RP-HPLC) purification. The optimized synthesis and purification process was complete in < 30 min and produced [ 11 C]nicotine with > 99.9% Radiochemical Purity (RCP), no [ 11 C]CH 3 I, no ( + ) nornicotine, 105 mCi/µmole specific activity, 7.0 – 7.2 pH, and 16.6% ethanol. The current method can be optimized, to reduce the ethanol content (<10%), and can be translated to a cGMP production of [ 11 C]nicotine for human clinical trials. [ABSTRACT FROM AUTHOR]

Given a hypercube Q n : = { 0 , 1 } n in R n and k ∈ { 0 , ... , n } , the k -th layer Q k n of Q n denotes the set of all points in Q n whose coordinates contain exactly k many ones. For a fixed t ∈ N and k ∈ { 0 , ... , n } , let P ∈ R [ x 1 , ... , x n ] be a polynomial that has zeroes of multiplicity at least t at all points of Q n ∖ Q k n , and P has zeros of multiplicity exactly t − 1 at all points of Q k n. In this short note, we show that d e g (P) ≥ max ⁡ { k , n − k } + 2 t − 2. Matching the above lower bound we give an explicit construction of a family of hyperplanes H 1 , ... , H m in R n , where m = max ⁡ { k , n − k } + 2 t − 2 , such that every point of Q k n will be covered exactly t − 1 times, and every other point of Q n will be covered at least t times. Note that putting k = 0 and t = 1 , we recover the much celebrated covering result of Alon and Füredi (1993) [1]. Using the above family of hyperplanes we disprove a conjecture of Venkitesh (2022) [23] on exactly covering symmetric subsets of hypercube Q n with hyperplanes. To prove the above results we have introduced a new measure of complexity of a subset of the hypercube called index complexity which we believe will be of independent interest. We also study a new interesting variant of the restricted sumset problem motivated by the ideas behind the proof of the above result. [ABSTRACT FROM AUTHOR]

A wide variety of applications are envisioned and demonstrated with artificial micro- and nanomachines, ranging from targeted drug or gene delivery, microsurgery, environmental sensing, and many more. Here, it is demonstrated how helical nanomachines can be used to measure and map the local mechanical properties of a complex heterogeneous environment. The positions of the nanomachines are precisely controlled using externally applied magnetic fields, while their instantaneous orientations provide estimation of the viscosity of the surrounding medium with high spatial and temporal accuracy. The measurement technique can be applied to both Newtonian as well as shear thinning media, and all experimental results are in good agreement with the theoretical analysis. It is believed that this novel application of helical nanomachines can be particularly relevant to biophysical studies and microfluidic technologies. [ABSTRACT FROM AUTHOR]

The present study aims to formulate a common synthetic strategy for preparing quantum dots (QDs) in a greener way by using combination of popular methods, viz. a colloidal method with suitable capping agent and low molecular weight gel based synthesis. Pyridine dicarboxylic acid (PDC) in presence of AlCl3 forms a stable metallogel, which serves as an excellent medium for selective ZnS QD synthesis. The aromatic pyridine moiety, well known for being a capping agent, indeed plays its part in the run up to QD synthesis. To the best of our knowledge, this is the first example of a metallogel based doped ZnS QD synthesis. Altering the doping material and its composition changes the properties of the QDs, but herein we also tried to establish how these changes affect the gel morphology and stability of both gel and QDs. We further demonstrate, by using live cell confocal microscopy, the delivery of QDs Cu ZnS and MnZnS nanomaterials in the nucleus and the cytoplasm of human breast cancer cells (MCF7), implicating the use of metallogel based QDs for bio-imaging and bio-labeling. [ABSTRACT FROM AUTHOR]

Camptothecin (CPT) selectively traps topoisomerase 1-DNA cleavable complexes (Top1cc) to promote anticancer activity. Here, we report the design and synthesis of a new class of neutral porphyrin derivative 5,10-bis(4-carboxyphenyl)-15, 20-bis(4-dimethylaminophenyl)porphyrin (compound 8) as a potent catalytic inhibitor of human Top1. In contrast to CPT, compound 8 reversibly binds with the free enzyme and inhibits the formation of Top1cc and promotes reversal of the preformed Top1cc with CPT. Compound 8 induced inhibition of Top1cc formation in live cells was substantiated by fluorescence recovery after photobleaching (FRAP) assays. We established that MCF7 cells treated with compound 8 trigger proteasome-mediated Top1 degradation, accumulate higher levels of reactive oxygen species (ROS), PARP1 cleavage, oxidative DNA fragmentation, and stimulate apoptotic cell death without stabilizing apoptotic Top1-DNA cleavage complexes. Finally, compound 8 shows anticancer activity by targeting cellular Top1 and preventing the enzyme from directly participating in the apoptotic process. [ABSTRACT FROM AUTHOR]

The receptor for advanced glycation end products (RAGE) at the blood-brain barrier (BBB) is critical for regulation of amyloid-β (Aβ) homeostasis in the diabetic brain. In this study, we used an in vitro BBB model consisting of mouse brain capillary endothelial cells (MBCECs) to investigate whether advanced glycation end products (AGEs) increase Aβ influx transport across the BBB and the underlying mechanisms. We found that AGEs induced Aβ influx transport across the BBB in concentration- and time-dependent manner, accompanied by increased RAGE expression and nuclear factor-kappa B p65 (NF-κB p65), and decreased nuclear peroxisome proliferator-activated receptor γ (PPARγ). Blockade of RAGE with its antibody and inhibition of NF-κB signaling with PDTC as well as activation of PPARγ with rosiglitazone significantly decreased Aβ transport across the BBB from the periphery to the brain. These treatments also pronouncedly suppressed AGEs-induced increases in RAGE expression and nuclear NF-κB p65 and reversed the decrease in nuclear PPARγ. These results suggest that RAGE-NF-κB-PPARγ signaling is involved in regulation of AGEs-induced influx transport of Aβ across the BBB and targeting the signaling pathway could serve as a novel strategy to modify such Aβ transport. [ABSTRACT FROM AUTHOR]

Objective: To compare the efficacy and safety of nadifloxacin and benzoyl peroxide versus adapalene and benzoyl peroxide in acne vulgaris. Materials and Methods: Patients fulfilling the inclusion criteria were divided into two groups. Patients in Group A received nadifloxacin and benzoyl peroxide. Patients in Group B received adapalene and benzoyl peroxide. Duration of treatment was 12 weeks. Changes in noninflammatory lesion count (NILC), inflammatory lesion count (ILC), total lesion count (TLC), investigator global assessment score (IGA) score, and Cardiff acne disability index (CADI) score was determined at weeks 0, 4, 8, and 12. Results: Combination of adapalene and benzoyl peroxide significantly decreased NILC, ILC, TLC, IGA score, and CADI score compared to the combination of nadifloxacin and benzoyl peroxide in acne vulgaris. Conclusion: Combination of adapalene and benzoyl peroxide is significantly more effective compared to the combination of nadifloxacin and benzoyl peroxide in the treatment of acne vulgaris. [ABSTRACT FROM AUTHOR]

A set D ⊆ V is called a k - tuple dominating set of a graph G = ( V , E ) if | N G [ v ] ∩ D | ≥ k for all v ∈ V , where N G [ v ] denotes the closed neighborhood of v . A set D ⊆ V is called a liar’s dominating set of a graph G = ( V , E ) if (i) | N G [ v ] ∩ D | ≥ 2 for all v ∈ V and (ii) for every pair of distinct vertices u , v ∈ V , | ( N G [ u ] ∪ N G [ v ] ) ∩ D | ≥ 3 . Given a graph G , the decision versions of k - Tuple Domination Problem and the Liar’s Domination Problem are to check whether there exist a k -tuple dominating set and a liar’s dominating set of G of a given cardinality, respectively. These two problems are known to be NP -complete (Liao and Chang, 2003; Slater, 2009). In this paper, we study the parameterized complexity of these problems. We show that the k - Tuple Domination Problem and the Liar’s Domination Problem are W[2] -hard for general graphs. It can be verified that both the problems have a finite integer index and satisfy certain coverability property. Hence they admit linear kernel as per the meta-theorem in Bodlaender (2009), but the meta-theorem says nothing about the constant. In this paper, we present a direct proof of the existence of linear kernel with small constants for both the problems. [ABSTRACT FROM AUTHOR]

Congenital diffuse infiltrating lipomatosis of the face (CDIL-F) is a rare and definite clinical entity of unknown etiology. It comprises a subgroup of lipomatous tumors. It is congenital in origin and occurs in infancy or in early childhood. CDIL-F is characterized by diffuse infiltration of mature adipose tissues over normal muscle fibers, rapid growth associated with osseous hyperplasia with a high recurrence rate after surgical intervention. Complte surgical excision is difficult due to diffuse infiltration and involvement of important facial structures. Till now, 14 cases have been reported in the literature. We report a case of CDIL-F in a 4-year old male child presenting with diffuse painlss swelling on right side of face. Ultrasonography, computed tomography and magnetic resonance imaging showed diffuse fat deposition in soft tissues in right malar region with thickening of right masseter muscl, fatty infiltration in right halfof tongue and osseous changes in right maxilla and right zygomatic arch. [ABSTRACT FROM AUTHOR]

Clerodendrum indicum (Lamiaceae) is a medicinally important shrub. We have studied the details of its pollination ecology which was hitherto unknown. The work was done during three consecutive years 2012-2014, based on 118 plants occurring in three widely separated wild populations in West Bengal, India, together with 25 individuals grown in an experimental plot. Details of flower structure and dynamics of floral events, pollen production and pollen dispersal, visitors and pollinators, floral attractants and floral rewards and pollen transfer mechanism have been worked out by standard methodologies with a 10x high resolution hand lens (IRL), a Leica WILD M3B Stereo-binocular microscope (Switzerland) and a Leica DMLB compound bright field light microscope (Germany). The tubular flower of four-day longevity attracts its visitors by visual cues. Flowers are visited regularly by ten species of insects. On the basis of the visitor behaviour, these can be classified into three distinct categories, viz., visitors belonging to Category-I act on cushion and trichome nectaries of calyx and corolla respectively, those of Category-II act on the dehisced anthers and trichome nectaries of corolla while those of Category-III act on dehisced anthers as well as receptive stigma. Majority of the visitors belong to either Category-I or Category-II. They visit only the 2nd day flowers and never visit a 3rd day flower when the stigma assumes receptivity. Therefore, they are not regarded as pollinators but, act as pollen and/or nectar robbers. Those are discriminated by offering secretions from extra-nuptial nectaries of the flower. Visitor species of Category-III, represented by a species of Trigona, constitute the legitimate pollinator of the plant and thereby, making the plant monophilic. Pollen presentation from the bisexual, dichogamous and protandrous flower takes place on the 2nd day, while the stigma assumes its receptivity on the 3rd day of flower opening. Pollen transfer to the body of the pollinator by a 2nd day flower in its male phase is achieved by offering edible pollen grains. On the other hand, a 3rd day flower at its female phase is devoid of the reward (pollen grain). The yellow shiny receptive stigma of such a flower strikingly mimics the freshly dehisced anthers and the pollinators being lured by such a stigma inadvertently transfer pollen onto it. C. indicum is so far the only known species of flowering plants where deceit pollination occurs by anther-mimicking stigma in a bisexual flower. [ABSTRACT FROM AUTHOR]

Plasma free fatty acids levels are increased in subjects with obesity and type 2 diabetes, playing detrimental roles in the pathogenesis of atherosclerosis and cardiovascular diseases. Increasing evidence showing that dysfunction of the vascular endothelium, the inner lining of the blood vessels, is the key player in the pathogenesis of atherosclerosis. In this review, we aimed to summarize the roles and the underlying mechanisms using the evidence collected from clinical and experimental studies about free fatty acid-mediated endothelial dysfunction. Because of the multifaceted roles of plasma free fatty acids in mediating endothelial dysfunction, elevated free fatty acid level is now considered as an important link in the onset of endothelial dysfunction due to metabolic syndromes such as diabetes and obesity. Free fatty acid-mediated endothelial dysfunction involves several mechanisms including impaired insulin signaling and nitric oxide production, oxidative stress, inflammation and the activation of the renin-angiotensin system and apoptosis in the endothelial cells. Therefore, targeting the signaling pathways involved in free fatty acid-induced endothelial dysfunction could serve as a preventive approach to protect against the occurrence of endothelial dysfunction and the subsequent complications such as atherosclerosis. [ABSTRACT FROM AUTHOR]

Introduction: Acute Otitis Media (AOM) is one of the frequently diagnosed diseases in children below two years. Amoxicillinclavulanate potassium is the first line drug in treatment of Paediatric AOM (PAOM). Cefpodoxime has good antimicrobial activity against various types of microorganisms that include causative microorganisms of PAOM. Aim: To compare the efficacy and safety of cefpodoxime and amoxicillin-clavulanate potassium for the treatment of PAOM in children below two years. Materials and Methods: A prospective longitudinal study was conducted on children diagnosed with PAOM. Thirty-six children were included in the study: 17 in the Group A (amoxicillinclavulanate potassium) and 19 in the Group B (cefpodoxime). Primary outcome of this study was clinical success rate at day 10 visit and secondary outcome was incidence of Adverse Events (AEs). Results: The clinical success rates were 93.8% in Group A and 88.2 % in Group B. These rates are comparable and no statistically significant difference was observed between the groups. Few mild and self-limiting AEs were observed and both the drugs were well tolerated. Conclusion: The results of this prospective study showed that a 10-day course of cefpodoxime is therapeutically comparable to amoxicillin-clavulanate potassium in terms of both efficacy and safety for the treatment of PAOM in children below two years. [ABSTRACT FROM AUTHOR]

We present the design and implementation of a new object-oriented simulation platform for a decentralized material handling system called the Coordinated Conveying System (CCS). CCS is a new approach to conveying entities, i.e., materials and people. It is also a generalized framework in which the connections between structure and behavior can be systematically studied. In this system, a collection of mobile units moves periodically along fixed tracks. Entities are transferred from some input to an output unit by the mobile units; entities can also transfer between mobile units during a space-time event called a rendezvous. This systems framework and model of conveying exposes a rich spectrum of spatio-temporal behaviors that have interesting connections to core issues in scheduling, resource allocation, communication, embedded systems, automation, and programming. The complexity of CCS arises from the interactions between the mobile units; hence, it is difficult to construct a system-level model for these dynamic behaviors, even though the behavior of individual units is simple. For these reasons, the simulator we present enables a systematic investigation of cyber-physical issues in CCS. Since all the details of CCS are not yet fully understood, we designed an extensible simulator using the Model-View-Controller architecture. The object-oriented approach helped us to model the CCS artifacts in a natural manner and, hence, reduced the complexity of our design. [ABSTRACT FROM AUTHOR]

Our previous studies showed that cysteinyl leukotrienes receptor 1 (CysLT 1 R) is upregulated in amyloid-β (Aβ)-induced neurotoxicity and that administration of CysLT 1 R antagonists such as pranlukast or montelukast can ameliorate memory impairment in mice. In the current study, we sought to explore the role of CysLT 1 R in intracerebroventricular streptozotocin (STZ-ICV)-induced mouse model of memory impairment and neuroinflammation through shRNA-mediated knockdown of CysLT 1 R and also its pharmacological blockade by pranlukast. ICR mice were infused with STZ (3.0 mg/kg) by a single bilateral stereotaxic ICV microinjection followed by administration of CysLT 1 R-shRNA (intra-hippocampal) or pranlukast (intragastric, IG). After 21 days, a set of behavioral and biochemical tests were performed in order to assess the degree of memory impairment and neuroinflammation in mice. STZ-infused mice spent less time in the target quadrant of Morris water maze test and took more time to find the shock-free arm in modified Y-maze test, which were rescued in the CysLT 1 R-knockdowned or pranlukast-treated mice. STZ-induced memory impairment was also accompanied by an elevated level of hippocampal CysLT 1 R, microglial activation, increased IL-1β, and TNF-α. Such elevation of these factors was found to be mediated through the classical NF-κB pathway and administration of CysLT 1 R-shRNA or pranlukast for 21 days reversed all these parameters, suggesting a role of CysLT 1 R in STZ-induced memory deficit and neuroinflammation. [ABSTRACT FROM AUTHOR]

Receptor-targeting radiolabeled molecular probes with high affinity and specificity are useful in studying and monitoring biological processes and responses. Dual- or multiple-targeting probes, using radiolabeled metal chelates conjugated to peptides, have potential advantages over single-targeting probes as they can recognize multiple targets leading to better sensitivity for imaging and radiotherapy when target heterogeneity is present. Two natural hormone peptide receptors, gastrin-releasing peptide (GRP) and Y1, are specifically interesting as their expression is upregulated in most breast and prostate cancers. One of our goals has been to develop a dual-target probe that can bind both GRP and Y1 receptors. Consequently, a heterobivalent dual-target probe, t-BBN/BVD15-DO3A (where a GRP targeting ligand J-G-Abz4-QWAVGHLM-NH2 and Y1 targeting ligand INP-K [ɛ-J-(α-DO3A-ɛ-DGa)-K] YRLRY-NH2 were coupled), that recognizes both GRP and Y1 receptors was synthesized, purified, and characterized in the past. Competitive displacement cell binding assay studies with the probe demonstrated strong affinity (IC50 values given in parentheses) for GRP receptors in T-47D cells (18 ± 0.7 nM) and for Y1 receptors in MCF7 cells (80 ± 11 nM). As a further evaluation of the heterobivalent dual-target probe t-BBN/BVD15-DO3A, the objective of this study was to determine its mouse and human serum stability at 37°C. The in vitro metabolic degradation of the dual-target probe in mouse and human serum was studied by using a 153Gd-labeled t-BBN/BVD15-DO3A and a high-performance liquid chromatography/radioisotope detector analytical method. The half-life (t1/2) of degradation of the dual-target probe in mouse serum was calculated as 7 hours and only ∼20% degradation was seen after 6 hours incubation in human serum. The slow in vitro metabolic degradation of the dual-target probe can be compared with the degradation t1/2 of the corresponding monomeric probes, BVD15-DO3A and AMBA: 15, and ∼40 minutes for BVD15-DO3A and 3.1 and 38.8 hours for AMBA in mouse and human serum, respectively. A possible pathway for in vitro metabolic degradation of the t-BBN/BVD15-DO3A in mouse serum is proposed based on the chromatographic retention times of the intact probe and its degradants. [ABSTRACT FROM AUTHOR]

Previously we reported that cysteinyl leukotrienes (Cys-LTs) and the type 1 receptor for Cys-LTs (CysLT 1 R) are related to amyloid β (Aβ)-induced neurotoxicity. The aim of the current study was to find out the role of CysLT 1 R on lipopolysaccharide (LPS)-induced cognitive deficit and neurotoxicity. shRNA-mediated knockdown or pharmacological blockade (by pranlukast) of CysLT 1 R were performed in ICR mice for 21 days prior to systemic infusion of LPS. From day 22, LPS was administered for 7 days and then a set of behavioral, histopathological and biochemical tests were employed to test memory, neuroinflammation and apoptotic responses in the mouse hippocampus. LPS (only)-treated mice showed poor performance in both Morris water maze (MWM) and Y-maze tests. However, shRNA-mediated knockdown or pranlukast-treated blockade of CysLT 1 R improved performance of the mice in these tests. To find out the possible underlying mechanisms, we assessed several parameters such as microglial activation (by immunohistochemistry), level of CysLT 1 R (by WB and qRT-PCR) and the inflammatory/apoptotic pathways (by ELISA or TUNEL or WB) in the mouse hippocampus. LPS-induced memory impairment was accompanied by activation of microglia, higher level of CysLT 1 R, IL-1β, TNF-α and nuclear NF-κB p65. LPS also caused apoptosis in the hippocampus as detected by TUNEL staining, further supplemented by detection of increased Caspase-3 and a reduced Bcl-2/Bax ratio. All of these adverse changes in the mouse hippocampus were inhibited by pretreatment with CysLT 1 R-shRNA and pranlukast. Through this study we suggest that CysLT 1 R shares a strong correlation with LPS-associated memory deficit, neuroinflammation and apoptosis and CysLT 1 R could be a novel target for preventive measures to intervene the progression of Alzheimer’s disease (AD)-like phenotypes. [ABSTRACT FROM AUTHOR]

Cysteinyl leukotrienes are a group of the inflammatory lipid molecules well known as mediators of inflammatory signaling in the allergic diseases. Although they are traditionally known for their role in allergic asthma, allergic rhinitis, and others, recent advances in the field of biomedical research highlighted the role of these inflammatory mediators in a broader range of diseases such as in the inflammation associated with the central nervous system ( CNS) disorders, vascular inflammation (atherosclerotic), and in cancer. Among the CNS diseases, they, along with their synthesis precursor enzyme 5-lipoxygenase and their receptors, have been shown to be associated with brain injury, Multiple sclerosis, Alzheimer's disease, Parkinson's disease, brain ischemia, epilepsy, and others. However, a lot more remains elusive as the research in these areas is emerging and only a little has been discovered. Herein, through this review, we first provided a general up-to-date information on the synthesis pathway and the receptors for the molecules. Next, we summarized the current findings on their role in the brain disorders, with an insight given to the future perspectives. [ABSTRACT FROM AUTHOR]

The neurodegeneration in AD patients may be associated with changes of peripheral immune responses. Some peripheral immune responses are altered due to neuroinflammation in colchicine induced AD (cAD) rats. The leaky blood brain barrier (BBB) in cAD-rats may be involved in inducing peripheral inflammation, though there is no report in this regard. Therefore, the present study was designed to investigate the role of BBB in cADrats by altering the BBB in a time dependent manner with injection (i.v.) of mannitol (BBB opener). The inflammatory markers in the brain and serum along with the peripheral immune responses were measured after 30 and 60 min of mannitol injection in cAD rats. The results showed higher inflammatory markers in the hippocampus and serum along with alterations in peripheral immune parameters in cAD rats. Although the hippocampal inflammatory markers did not further change after mannitol injection in cAD rats, the serum inflammatory markers and peripheral immune responses were altered and these changes were greater after 60 min than that of 30 min of mannitol injection. The present study shows that the peripheral immune responses in cAD rats after 30 and 60 min of mannitol injection are related to magnitude of impairment of BBB in these conditions. It can be concluded from this study that impairment of BBB in cAD rats is related to the changes of peripheral immune responses observed in that condition. [ABSTRACT FROM AUTHOR]

Introduction: Diabetic dyslipidaemia poses a therapeutic challenge. New therapies have emerged in this patient subgroup to enhance outcome and improve compliance. Aim: The aim of this study was to compare the effectiveness and safety of add on therapy of saroglitazar and fenofibrate with metformin in Indian patients with diabetic dyslipidaemia. Materials and Methods: Adults patients with diabetic dyslipidaemia fulfilling the inclusion criteria were randomized in two groups. Group A patients received metformin (1000 mg/ day) and fenofibrate (160 mg/day) while group B patients received metformin (1000 mg/day) and saroglitazar (4 mg/ day). Glycosylated haemoglobin (HbA1C), triglyceride (TG), LDL- cholesterol (LDL-C), HDL-cholesterol (HDL-C) levels were measured at baseline and week 12 visits. Fasting plasma glucose (FPG) and post prandial plasma glucose (PPPG) were measured at baseline and on week 4, 8 and 12 visits. Results: TG and HbA1C levels decreased significantly at week 12 from their respective baseline values (p< 0.05) in both groups. FPG and PPPG levels significantly decreased at weeks 4, 8 and 12 compared to their pretreatment values (p< 0.05) in both groups. TG and HbA1C levels in group B decreased significantly compared to group A at week 12. FPG and PPPG levels in group B also decreased significantly compared to group A at every interval. Inter group analysis did not show any statistically significant change in body weight, LDL-C and HDL-C at week 12. Conclusion: Add on therapy of saroglitazar with metformin significantly decreased TG, HbA1C, FPG and PPPG levels compared to add on therapy of fenofibrate with metformin in Indian patients with diabetic dyslipidaemia. [ABSTRACT FROM AUTHOR]

Background: Allergic rhinitis (AR) is a very common worldwide problem; patients display a number of symptoms, such as sneezing, nasal itching, and rhinorrhea, and their lifestyle is affected. Desloratadine is a novel, long-acting inhibitor of histamine. However, very little is known about the effect of desloratadine citrate disodium injection (DLC injection) on AR, and the underlying mechanisms are yet unexplored. Herein, we sought to explore the effects and mechanisms of actions of DLC injection in ovalbumin (OVA)-induced immune responses in a rat model of AR. Methods: Sixty rats were subjected to immunization with OVA (intraperitoneal [IP]), followed by a nasal challenge with OVA. Drugs or saline were given daily for treatment. Nasal symptoms and histology of the nasal mucosa were examined. Cytokines such as interleukin (IL)-4, IL-12, interferon (IFN)-γ, adhesion molecules such as soluble vascular cell adhesion molecule 1 (sVCAM-1), and inducible nitric oxide synthase (iNOS) expression were assessed by enzymelinked immunosorbent assay (ELISA) kit. Nitric oxide (NO) concentration was also measured by NO assay kit. Results: DLC treatment (intravenous [IV]) significantly decreased the frequency of sneezing and nasal scratching and alleviated nasal inflammation by increasing the serum levels of IFN-γ and IL-12, while lowering the expression of IL-4. Thus, DLC (IV) treatment led to a marked elevation in Thelper 1/T-helper 2 (Th1/Th2) ratio when administered in the AR rats. The expression of sVCAM-1, iNOS, and NO were also reversed. Conclusion: DLC (IV), given after an allergen challenge, improved Th1 cytokines level and restrained Th2 responses alleviating the symptoms of AR. Our results indicate that DLC injection may exhibit such effects through the modulation of T-cell responses. [ABSTRACT FROM AUTHOR]

Correlated Color Temperature (CCT) is an important parameter to determine the quality of lighting in an indoor space. We have presented here the calibration of RGB sensor for estimation of real-time CCT values using Support Vector Machine Regression, General Regression Neural Network, and Gaussian Process Regression techniques. Further, comparative performance assessment have been done on the evaluating parameters: Percentage Absolute Error, R-Squared Error, Mean Absolute Error, Mean Absolute Percentage Error, and Root Mean Squared Error with respect to a calibrated meter. The RGB values have been acquired from a sensor interfaced with a microcontroller and the CCT data are simultaneously observed from a calibrated chroma meter at the client terminal. The machine learning regression techniques have been applied at the server terminal to find out the CCT values and a comparative performance analysis have been done to find the best possible prediction model that can be compared to a standard meter based on the performance indices to decide on their accuracy. [ABSTRACT FROM AUTHOR]

While the ordering of amino acidsin proteins and peptide-basedmaterials is known to affect their folding patterns and supramoleculararchitectures, tailoring self-assembly behavior in stimuli responsivepeptides by isomerizing a peptide sequence has not been extensivelyexplored. Here, we show that changing the position of a single hydrophobicamino acid in short amphiphilic peptides can dramatically alter theirpH-triggered self-assembly transitions. Using palmitoyl-IAAAEEEE-NH2and palmitoyl-IAAAEEEEK(DO3A:Gd)-NH2as controls,moving the Isoleucine away from the palmitoyl tail preferentiallyinduces nanofiber formation over spherical micelles. Shifting theIsoleucine one residue away makes the transition pH more basic by2 units. When in the third or fourth position, nanofibers are formedexclusively above 10 μM. We propose that moving the Isoleucineaway from the tail enhances its ability to promote β-sheet formationinstead of folding back into the palmitoyl core. These findings reveala novel strategy for programming pH-triggered self-assembly by isomerizinga peptide sequence. [ABSTRACT FROM AUTHOR]

There has been recent interest indesigning smart diagnostic ortherapeutic self-assembling peptide or polymeric materials that canselectively undergo morphological transitions to accumulate at a diseasesite in response to specific stimuli. Developing approaches to probethese self-assembly transitions in environments that accurately amalgamatethe diverse plethora of proteins, biomolecules, and salts of bloodis essential for creating systems that function in vivo. Here, we have developed a fluorescence anisotropy approach to probethe pH-dependent self-assembly transition of peptide amphiphile (PA)molecules that transform from spherical micelles at pH 7.4 to nanofibersunder more acidic pH’s in blood serum. By mixing small concentrationsof a Ru(bipy)32+-tagged PA with a Gd(DO3A)-taggedPA having the same lipid–peptide sequence, we showed that thepH dependence of self-assembly is minimally affected and can be monitoredin mouse blood serum. These PA vehicles can be designed to transitionfrom spherical micelles to nanofibers in the pH range 7.0–7.4in pure serum. In contrast to the typical notion of serum albuminabsorbing isolated surfactant molecules and disrupting self-assembly,our experiments showed that albumin does not bind these anionic PAsand instead promotes nanofibers due to a molecular crowding effect.Finally, we created a medium that replicates the transition pH inserum to within 0.08 pH units and allows probing self-assembly behaviorusing conventional spectroscopic techniques without conflicting proteinsignals, thus simplifying the development pathway from test tube to in vivoexperimentation for stimuli-responsive materials. [ABSTRACT FROM AUTHOR]

COVID-19 has destabilized economies, lives all over the globe with devastating impacts. Physical and mental health suffered hugely due to this pandemic. Moreover, educational institutes were forced to shift from offline to online mode. This study aims to identify critical societal constructs which got impacted due to the COVID-19 pandemic in India and Bangladesh. Further, a comparative analysis has been carried out to assess these impacts between these two countries from a social science point of view. A cross-sectional study has been conducted through a structured questionnaire based on pilot study. Google Survey form link of questionnaire was active from March 15, 2020 to July 14, 2020 in which 1023 responses were received with a response rate of 54%. After the elimination of missing responses, 802 complete responses were finally coded on 48 variables including demographic profile of the respondents. Factor analysis is used to identify critical constructs of the study whereas hypothesis testing to carry out for comparative understanding. The study found that COVID-19 pandemic has severely impact on psychological, educational, economic, and social aspects of both countries whereas Bangladesh has significant adverse impact than India. Economic stimulus program such as tax exemption, EMI moratoriums, mental health training, E-learning, low interest rate of soft loan disbursement are noteworthy requirement to overcome the adverse impact of COVID-19. [ABSTRACT FROM AUTHOR]

Blood-brain barrier (BBB) impairment in systemic inflammation leads to neuroinflammation. Several factors including cytokines, chemokines and signal transduction molecules are implicated in BBB dysfunction in response to systemic inflammation. Here, we have adopted a novel in vivo technique; namely, cerebral open flow microperfusion (cOFM), to perform time-dependent cytokine analysis (TNF-alpha, IL-6 and IL-10) in the frontal cortex of the rat brain in response to a single peripheral administration of lipopolysaccharide (LPS). In parallel, we monitored BBB function using sodium fluorescein as low molecular weight reporter in the cOFM sample. In response to the systemic LPS administration, we observed a rapid increase of TNF-alpha in the serum and brain, which coincides with the BBB disruption. Brain IL-6 and IL-10 synthesis was delayed by approximately 1 h. Our data demonstrate that cOFM can be used to monitor changes in brain cytokine levels and BBB disruption in a rat sepsis model. [ABSTRACT FROM AUTHOR]

Abstract: Detailed structural analysis of the X-Ray diffraction pattern of La0.9Gd0.1FeO3 (LGFO) synthesized via the solid state reaction reveals distorted perovskite structure. Magnetization studies show a characteristic of weak ferromagnetism which is believed to be induced by canted anti-ferromagnetically coupled spins. When explored in a wide temperature and frequency range, AC electrical properties reveal interesting relaxation mechanisms. LGFO exhibits relatively high dielectric permittivity (ε′~4×103) close to room temperature. Temperature dependent magneto-dielectric response appears (magnetodielectric ~−5.5%) even at low magnetic field ~5kOe. Attractive electrical, magnetic and magnetoelectric properties of the present LGFO at relatively higher temperature makes it a very promising material for application in devices. [Copyright &y& Elsevier]