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The manufacturing of fossil-based fertilizers by extraction of rock phosphate has contributed to carbon emissions and depleted the non-renewable phosphorus reserves. Sewage sludge, which is a waste product from Sewage Treatment Plants (STPs), is rich in phosphorus. The existing techniques for sludge management contribute to carbon emissions and ecological footprint. Struvite (raw fertilizer) and biochar recovery from sludge has emerged as viable methods to reduce carbon emission and ensure economic sustainability of STPs. In this work, the potential for phosphorus recovery and revenue generation is discussed for Rajasthan state in India. The fate of phosphorus and heavy metals in STPs is evaluated which indicates that about 70% of the phosphorus and trace amounts of metals end up in sewage sludge. Further, the power consumption is high in STPs due to industrial wastewater ingress. There is a need to bridge the gap between sewage treatment and generation in Rajasthan, improve STP performance before resource recovery inclusion at policy-level and scale-up. Mixing struvite with biochar can lead to safe application of struvite as raw fertilizer as heavy metals are sequestered by biochar. A business framework is developed to serve as a blueprint and potential model for linking technical and market viability. HIGHLIGHTS This article highlights the concept of integrated sewage management for conforming to discharge guidelines and resource recovery from sewage sludge.; The present policies for wastewater management in India are discussed.; The carbon footprint and revenue generation from struvite and biochar are discussed.; A business framework has been developed.; The fate of phosphorus and heavy metals in STPs is evaluated.;

Introduction: This study aimed to explore the relationship between craniofacial anthropometric measurements and personality traits among medical students. Understanding these associations could provide novel insights into how physical characteristics relate to psychological dimensions. Methodology: A cross-sectional study was conducted at Jawahar Lal Nehru Medical College, DMIMS, Wardha, India, involving 295 participants (130 males, 165 females) aged 18–30 years. Craniofacial measurements, including forehead length, bizygomatic width, and cephalic index, were obtained using calibrated instruments. Personality traits were assessed using the Big Five Personality Test. Data analysis included Pearson’s correlation and regression models, with p

R-spondins are secretory proteins localized in the endoplasmic reticulum and Golgi bodies and are processed through the secretory pathway. Among the R-spondin family, RSPO2 has emanated as a novel regulator of Wnt signaling, which has now been acknowledged in numerous in vitro and in vivo studies. Cancer is an abnormal growth of cells that proliferates and spreads uncontrollably due to the accumulation of genetic and epigenetic factors that constitutively activate Wnt signaling in various types of cancer. Colorectal cancer (CRC) begins when cells in the colon and rectum follow an indefinite pattern of division due to aberrant Wnt activation as one of the key hallmarks. Decades-long progress in research on R-spondins has demonstrated their oncogenic function in distinct cancer types, particularly CRC. As a critical regulator of the Wnt pathway, it modulates several phenotypes of cells, such as cell proliferation, invasion, migration, and cancer stem cell properties. Recently, RSPO mutations, gene rearrangements, fusions, copy number alterations, and altered gene expression have also been identified in a variety of cancers, including CRC. In this review, we addressed the recent updates regarding the recurrently altered R-spondins with special emphasis on the RSPO2 gene and its involvement in potentiating Wnt signaling in CRC. In addition to the compelling physiological and biological roles in cellular fate and regulation, we propose that RSPO2 would be valuable as a potential biomarker for prognostic, diagnostic, and therapeutic use in CRC.

Prostate cancer, or PCa, is a prominent male malignancy. For men with prostate cancer, accurate staging is essential for planning treatment and determining the prognosis. The way prostate cancer is currently diagnosed has led to two types of problems: overdiagnosis, which results in overtreatment, and underdiagnosis, which leads to missed diagnoses. Multiparametric magnetic resonance imaging (mpMRI) could assist in reducing prostate cancer diagnosis errors. Automatic prostate cancer techniques often use deep learning or machine learning to identify the lesion or tumor. Even after using these methods, they are not accurate every time in detecting and identifying prostate tumors after giving multiple sequences of mpMRI as input. Due to the absence of a clinically established test dataset, the output of the automatic prostate cancer system is extremely hard to verify. With the help of Explainable Artificial Intelligence (XAI) and expert review, the results of automatic prostate cancer techniques can be verified.

The study aims to determine the inheritance pattern of different morphological features of the external ear in three generations from five states of India to assess the similarities between P1, F1, and F2 generations. The research involved 62 families, each with 124 grandparents P1 (62 males and 62 females), 124 parents F1 (62 males and 62 females), and 82 F2 generations (53 males and 29 females), a total of 330 samples, ranging in age from 1 to 75 years. All the samples were collected from five different states of India: Uttar Pradesh, Madhya Pradesh, Rajasthan, Bihar and Maharashtra. The external ear is distinct in terms of shape, size, and orientation. Its morphological variation aids in the determination of genetic inheritance. Fisher exact test was performed to assess the inter-generation association of morphological characteristics of the ear. Similar to other body characteristics, it is established that the auricle shape, lobule shape, and ear lobule attachment are also inherited. The associations of ear traits in three generations were studied, and the results might be used in forensic identification.

Abstract Background The scientific and technological advances along with the changing socio-economical standards of society have posed new challenges to the criminal justice system. With the changes in society and technology, there is also an increase in crime rate. Forensics provides the scientific proofs beyond the shadow of reasonable doubt and thus significantly contributes in criminal as well as civil investigations and legal matters. Main body of the abstract Discovery of DNA has opened new avenues and the advancement of DNA technology and its introduction into the court of law has provided extensive aid in the resolution of civil and criminal disputes. In India, the DNA technology was first introduced in a paternity dispute in 1989. However, the need for legislation and guidelines to support grounds for the use of DNA profiling for forensic purposes in India has been recognized for some time now. In July 2019, the DNA Technology (Use and Application) Bill 2019 was introduced in the Indian parliament. Short conclusion Herein, this article is focused on the current aspects of DNA based evidence in the Indian Criminal Justice system along with the associated issues, highlighting the need for specific DNA based legislation.

The Citizenship Amendment Act 2019 and the National Register of Citizens in India are perceived as reflective of a religious classification in grant and continuance of Indian citizenship. The study aimed to discuss the future effects of the amended Citizenship Act 2019 and suggest alternatives to accommodate India's constitutional ethos. A considerable fraction of the Indian citizenry was discorded with this Act because Article 14 of the Indian Constitution prohibits discrimination based on religion, among other grounds. On the other hand, the state's stance asserted that the law aims to protect the persecuted religious minorities from other states. This study dealt with the nuances and intricacies of the problem to explicate viable solutions by an in-depth analysis of the issue in an unprejudiced manner where it used a combined doctrinal and empirical research to assess the perspectives on the policy in the Global South from the Indian experience. The findings reflected that while a majority of the provisions in the Act can be justified based on constitutional parameters, its few provisions are unconstitutional. In summary, even after juxtaposing all the justifications of the Act against the allegations, a considerable portion of the Act remains unconstitutional, and it needs to be revisited based on constitutional parameters.

Introduction: Physiognomic evaluation of the human face has been widely considered in computer-based visual applications, to know the characteristic properties of human. This had given rationality for the present study to be planned on craniofacial anthropometry and its relationship with personality traits in medical students. Aim: Evaluate the effectiveness of different craniofacial anthropometry; cephalic index, forehead width, forehead length, bizygomatic width, bigonial width, upper facial index, and facial index with the type of personality traits and impact of metacognitive and emotional interventions on personality among medical students. Materials and Methods: A cross-sectional interventional analytical study on Bachelor of Medicine and Bachelor of Surgery (MBBS) undergraduate students with sample size of 293 will be conducted in Jawahar Lal Nehru Medical College, DMIMS, Wardha, Maharashtra, India. The age group of samples will be 18-30 years. The expected duration of study will be August 2022 to July 2025. The data collection will be carried out for a period of one and half year (January 2023 to June 2024). The tools for data collection shall be craniofacial anthropometric measurement, Big Five Personality Test (BFPT) questionnaire, meta- cognitive awareness inventory, Emotional Intelligence self-assessment Questionnaire (EIQ), Personal information Questionnaire (PIQ). Expected results: The results will be drawn by comparing Craniofacial Anthropometric Measurement with personality traits and effect of metacognitive and emotional intervention. Conclusion: The present study will be also a torchbearer for medical teachers and psychologist and behavioural medicine to understand individual’s personality by face cueing.

Aim The present study was designed to explore the STR diversity and genomic history of the inhabitants of the most populous subdivision of the country. A set of 24 hypervariable autosomal STRs was used to estimate the genetic diversity within the studied population. A panel of 15 autosomal STRs, which is most common in the previously reported data sets, was used to estimate the genetic diversity between the studied population, and obtained unique relations were reported here. Method The genetic diversity and polymorphism among 636 individuals of different ethnic groups, residing in Bareilly, Pilibhit, Shahjahanpur, Gorakhpur, Jhansi, and Varanasi regions of Uttar Pradesh, India, was investigated. This investigation was carried out via 24 autosomal STRs. Result The 24 loci studied showed the highest value of combined power of discrimination (CPD = 1), combined power of exclusion (CPE = 0.99999999985), combined paternity index (CPI = 6.10 × 109) and lowest combined matching probability (CPM = 7.90 × 10−31). Conclusion The studied population showed genetic closeness with the population of Uttarakhand, the Jats of Delhi,the Jat Sikh (Punjab), and the population of Rajasthan. Among the tested loci, SE33 and Penta E were found to be most useful in terms of the highest discrimination power, lowest matching probability, the highest power of exclusion, and highest polymorphism information content for the Uttar Pradesh population .

Background Most of the forensic DNA laboratories have migrated to new generation STR kits of 6 dye chemistry with more than 20 autosomal STRs. The population-specific databases of such STR markers are lacking in many regions. Aim To evaluate the effect of the inter-population database in 100 paternity trios with no inconsistencies at 23 STRs. Subjects and methods 100 paternity trios were evaluated considering inter-population allelic frequency values for calculation of Combined Paternity Index (CPI) and Probability of Paternity (POP). Results No significant variation (p

Background Though microvariant alleles are widely reported in global populations, they are not well characterised to date. Aim To study the prevalence and characterisation of size and sequence-based microvariant alleles Subjects and methods Next Generation Sequencing (NGS) was used to sequence microvariant alleles at nine autosomal STR markers in 138 samples. Results After sequencing 31 STR markers using Precision ID GlobalFilerTM NGS STR panel v2, only nine markers, i.e. D12S391, D19S433, D1S1656, D21S11, D2S441, D7S820, FGA, Penta D, and TH01 showed the prevalence of microvariant alleles. Occurrence of microvariant alleles was positively correlated with Total Possible Alleles (p

The human skin is a complex organ that forms the first line of defense against pathogens and external injury. It is composed of a wide variety of cells that work together to maintain homeostasis and prevent disease, such as skin cancer. The exponentially rising incidence of skin malignancies poses a growing public health challenge, particularly when the disease course is complicated by metastasis and therapeutic resistance. Recent advances in single-cell transcriptomics have provided a high-resolution view of gene expression heterogeneity that can be applied to skin cancers to define cell types and states, understand disease evolution, and develop new therapeutic concepts. This approach has been particularly valuable in characterizing the contribution of immune cells in skin cancer, an area of great clinical importance given the increasing use of immunotherapy in this setting. In this review, we highlight recent skin cancer studies utilizing bulk RNA sequencing, introduce various single-cell transcriptomics approaches, and summarize key findings obtained by applying single-cell transcriptomics to skin cancer.

Body fluids such as blood, semen, saliva, and vaginal secretions are commonly encountered as biological evidences at the scene of crime. Tears are rarely encountered and largely unexplored in the forensic context. Analysis of body fluid evidence helps in establishing a link between the perpetrator, victim, and crime scene for reconstruction. Several methods exist for their identification using biochemical and serological methods. But due to their limitation as destructive techniques and low specificity, they are prone to give false-positive results. On contrary, Attenuated Total Reflectance Fourier Transform Infrared (ATR-FTIR) spectroscopy has been explored due to its ability to identify unknown substances based on their molecular structure. The present study investigated the use of ATR-FTIR spectroscopy for the detection and discrimination of tears from other commonly encountered body fluids. The study also investigated the potential of tears as an age estimation marker at the scene of crime. The results depicted that chemometric methods successfully discriminate the infrared spectra of tears from the other fluids with 100% accuracy, while the spectra of tears showed significant changes over time and the regression model showed that it can be used for age estimation at the scene of crime. The overall findings of this study can be further used in crime scene investigation after more rigorous investigation and validation under several interfering factors.

Introduction: Frontline Healthcare Workers (F-HCWs) are at the front position for medical care against Coronavirus Disease 2019 (COVID-19) pandemic which has life-threatening potentials. Poor level of knowledge, practices and negative attitudes as well as high-risk of psychological distress among F-HCWs can directly lead to delayed diagnosis, treatment and poor infection control practices. Aim: To assess the level of Knowledge, Attitude and Practices (KAP) as well as risk of psychological distress among F-HCWs for COVID-19 pandemic. Materials and Methods: This descriptive, hospital-based, cross-sectional study was conducted at Government Medical College, Azamgarh, Uttar Pradesh, India, located in a tertiary care centre in rural area from October 2021 to December 2021 among 223 F-HCWs using convenient sampling technique. To assess the level of KAP as well as risk of psychological distress among F-HCWs, a prevalidated structured questionnaire was used consisting of 15 knowledge questions, six attitude questions, 15 practices questions and six questions on risk of psychological distress. Chi-square test was performed to examine the association between risk of psychological distress and level of KAP as well as with demographic characteristics of F-HCWs. Results: Out of total 223 participants more than half of the physicians (52.9%) and one-third of staff nurses (35.9%) were from age group of 25-35 years, respectively. Majority of both physicians (57.1%) and staff nurses (87.6%) were married and had nuclear type of family, accounting for 64.3% and 74.5%, respectively. Most of the physicians (92.9%) had good level of knowledge but they had less positive attitude (84.3%) compared to staff nurses (92.8%). Majority of both physicians (64.3%) and staff nurses (58.2%) had no or low risk of psychological distress, while only a few of them had high level of risk. Conclusion: In this study, majority of F-HCWs reported overall ‘good’ level of KAP for prevention of COVID-19. As for risk of psychological distress was concerned, majority of F-HCWs had no or low risk.

The digital economy and multi-faceted markets have significantly contributed to the efficacy of most transactions governing modern humankind. Digital platforms have become an irreplaceable cross-border asset that has acclimatized with technological advancements. However, there is obscurity in the methods of accommodation of digital economy in competition laws of most jurisdictions globally. Consequently, there are ascertainable issues in competition laws of such jurisdictions. Such issues remain unaddressed due to the absence of evaluation parameters of digital platforms in the conventional market system and culminate into an Implicit and undetected abuse of dominance. This study used the doctrinal method by highlighting the distinctness of contemporary digital markets and their consequential issues. This study explicated the issues in the competition that need to be independently addressed, considering the intricacies of digital platforms. The presence of non-price factors, multi-faceted markets, and data-driven networks being the primary source of such novel issues have been particularly explicated. The established premise was substantiated by way of case studies of major events involving factors such as predation, deep discounting, and data privacy. Elucidation of the competition system in most jurisdictions in Asia and the accommodation of digital platforms in the same was also sufficiently enunciated to present a holistic insight to the established premise. Finally, the authors suggested ways to sufficiently address the issues arising from the distinctness of digital platforms, thereby giving rise to a dynamic and all-inclusive competition.

Abstract The ex-vivo biochemical changes of different body fluids also referred as aging of fluids are potential marker for the estimation of Time since deposition. Infrared spectroscopy has great potential to reveal the biochemical changes in these fluids as previously reported by several researchers. The present study is focused to analyze the spectral changes in the ATR-FTIR spectra of three body fluids, commonly encountered in violent crimes i.e., semen, saliva, and urine as they dry out. The whole analytical timeline is divided into relatively slow phase I due to the major contribution of water and faster Phase II due to significant evaporation of water. Two spectral regions i.e., 3200–3400 cm−1 and 1600–1000 cm−1 are the major contributors to the spectra of these fluids. Several peaks in the spectral region between 1600 and 1000 cm−1 showed highly significant regression equation with a higher coefficient of determination values in Phase II in contrary to the slow passing Phase I. Principal component and Partial Least Square Regression analysis are the two chemometric tool used to estimate the time since deposition of the aforesaid fluids as they dry out. Additionally, this study potentially estimates the time since deposition of an offense from the aging of the body fluids at the early stages after its occurrence as well as works as the precursor for further studies on an extended timeframe.

Abstract Background Assays that specifically measure α‐synuclein seeding activity in biological fluids could revolutionize the diagnosis of Parkinson’s disease. Recent improvements in α‐synuclein real‐time quaking‐induced conversion assays of cerebrospinal fluid have dramatically reduced reaction times from 5‐13 days down to 1‐2 days. Objective To test our improved assay against a panel of cerebrospinal fluid specimens from patients with Parkinson’s disease and healthy controls from the MJ Fox Foundation/NINDS BioFIND collection. Methods Specimens collected from healthy controls and patients with clinically typical moderate‐to‐advanced Parkinson’s disease were tested without prior knowledge of disease status. Correlative analyses between assay parameters and clinical measures were performed by an independent investigator. Results BioFIND samples gave positive signals in 105/108 (97%) Parkinson’s disease cases versus 11/85 (13%) healthy controls. Receiver operating characteristic analyses of diagnosis of cases versus healthy controls gave areas under the curve of 95%. Beyond binary positive/negative determinations, only weak correlations were observed between various assay response parameters and Parkinson’s disease clinical measures or other cerebrospinal fluid analytes. Of note, REM sleep behavioral disorder questionnaire scores correlated with the reaction times needed to reach 50% maximum fluorescence. Maximum fluorescence was inversely correlated with Unified Parkinson's Disease Rating Scale motor scores, which was driven by the patients without REM sleep behavioral disorder. Conclusions Our improved α‐synuclein seed amplification assay dramatically reduces the time needed to diagnose Parkinson’s disease while maintaining the high‐performance standards associated with previous α‐synuclein seed assays, supporting the clinical utility of this assay for Parkinson’s disease diagnosis.

Abstract Objective This study was planned to evaluate the genetic diversity in the admixed and Teli (a Hindu caste) populations of Maharashtra, India using 20 autosomal Short Tandem Repeat (STR) genetic markers. We further investigated the genetic relatedness of the studied populations with other Indian populations. Results The studied populations showed a wide range of observed heterozygosity viz. 0.690 to 0.918 for the admixed population and 0.696 to 0.942 for the Teli population. This might be due to the multi-directional gene flow. The admixed and Teli populations also showed a high degree polymorphism which ranged from 0.652 to 0.903 and 0.644 to 0.902, respectively. Their combined value of matching probability for all the studied loci was 4.29 × 10–25 and 5.01 × 10–24, respectively. The results of Neighbor-Joining tree and Principal Component Analysis showed that the studied populations clustered with the general populations of Jharkhand, UttarPradesh, Rajasthan and Central Indian States, as well as with the specific populations of Maharashtra (Konkanastha Brahmins) and Tamil Nadu (Kurmans). Overall, the obtained data showed a high degree of forensic efficacy and would be useful for forensic applications as well as genealogical studies.

Introduction: Competency-Based Medical Education (CBME) is newly transformed education system in India to enhance five major qualities in doctors like, clinician, communicator, leader, life-long learner and professional. The CBME was launched in 2019 in all Medical Institution of India to uniform one’s knowledge, skills and a new domain Affection but this newly reformed system need hike in manpower, infrastructure, budget and technology which is a dilemmatic thought. Aim: To perceive the acceptance of the faculty participants about CBME system and also to explore various domains including the efficiency of training orientation/sensitisation, sufficiency of knowledge about CBME, infrastructure, manpower and finance required and strategies or implementation. Materials and Methods: This cross-sectional study was conducted in Government Medical College, Azamgarh, Uttar Pradesh, India, from January 2020 to July 2020. Total 60 participants were included in the study. The study used a validated set of questions about CBME. The assessed domains were competency definition, difference between traditional and new curriculum, merits and demerits of CBME, stages of competence and strategies to implement. Descriptive statistics were used to describe the data using Microsoft Excel. Results: Total 60 (39 trained+21 untrained faculty) were included in the study, with maximum 28 (46.67%) were aged between 30-40 years {males were 38 (63.33%) and 22 (36.67%) were females}. Total 37 faculties knows “what is competency”, 37 participants responded for difference between CBME and traditional Medical education, 22 participants responded for stages of competency, 22 responded on steps and strategy for its implementation, 38% answered on merits and demerit of current curriculum. Conclusion: The sufficiency of knowledge of CBME can be easily judged by proportion of responses of open ended questions which was not more than 50% faculty for all questions. Closed ended questions have suggested that infrastructure, manpower and finance are not up to mark to implement CBME.

Herein, we report on mechanical deformation of single-crystal Ti2AlC MAX phase using compression testing of micropillars with a range of crystallographic orientations. Our results show that depending on the crystallographic orientation, the Ti2AlC micropillars either undergo only non-classical (non-Schmid) crystallographic slip, non-classical crystallographic slip followed by cleavage or cleavage without any appreciable crystallographic slip. The non-classical crystallographic slip is found to be a result of the strong dependence of crystallographic slip on both, the resolved shear stress and the stress normal to the slip plane.

Previously, we demonstrated an integrated genomic convergence and network analysis approach to identify the candidate genes associated with the complex neurodegenerative disorder, Alzheimer’s disease (AD). Here, we performed a pilot study to validate the in silico approach by studying the association of genetic variants from three identified critical genes, APOE, EGFR, and ACTB, with AD. A total of 103 patients with AD and 146 healthy controls were recruited. A total of 46 single-nucleotide polymorphisms (SNPs) spanning the three genes were genotyped, of which only 19 SNPs were included in the final analyses after excluding non-polymorphic and Hardy–Weinberg equilibrium-violating SNPs. Apart from our previously reported APOE ε4, four other SNPs in APOE (rs405509, rs7259620, −rs769449, and rs7256173), one in EGFR (rs6970262), and one in ACTB (rs852423) showed a significant association with AD (p < 0.05). Our results validate the reliability of genomic convergence and network analysis approach in identifying the AD-associated candidate genes.

Materials design calls for an optimal exploration and exploitation of the process-structure-property (PSP) relationships to produce materials with targeted properties. Recently, we developed and deployed a closed-loop multi-information source fusion (multi-fidelity) Bayesian Optimization (BO) framework to optimize the mechanical performance of a dual-phase material by adjusting the material composition and processing parameters. While promising, BO frameworks tend to underperform as the dimensionality of the problem increases. Herein, we employ an adaptive active subspace method to efficiently handle the large dimensionality of the design space of a typical PSP-based material design problem within our multi-fidelity BO framework. Our adaptive active subspace method significantly accelerates the design process by prioritizing searches in the important regions of the high-dimensional design space. A detailed discussion of the various components and demonstration of three approaches to implementing the adaptive active subspace method within the multi-fidelity BO framework is presented.

Background: It is difficult to approach the Trigeminal Ganglion (TG) and Meckel's cave (MC) during surgeries. Therefore, the exact knowledge of the relationship of surgical landmarks to related anatomical structures is vital to reduce the associated postoperative morbidity. The aim of the present study was to enhance the knowledge of the surgical anatomy of structures that are present in the conduit of all surgical approaches to TG and MC, their distances from surrounding neurovascular structures, and their variations. Material and Methods: The study was carried out on 40 embalmed cadavers (Eight Female) of the anatomy department of a teaching hospital in Central India. Meticulous dissection of cranial fossae was done to locate TG, MC, and related anatomical structures. All distances from TG and MC were measured using an electronic digital calliper. Results: Length, width, and thickness of TG were 15.39 mm, 4.39 mm, and 2.54 mm, respectively. The distance from zygomatic arch, the lateral end of the petrous ridge, arcuate eminence, foramen ovale, and foramen spinosum to MC was 26.10 mm and 37.94 mm, 16.46 mm, 4.54 mm, and 11.23 mm, respectively. The sixth, fourth, and third cranial nerves were 6.26 mm, 4.94 mm, and 2.53 mm from MC, respectively. The MC was 42.72 mm and 33.87 mm anteromedial from posterior and anterior limits of the sigmoid sinus. Conclusion: Findings of the present study will aid surgical planning and decide the approach to TG and MC and avoid surgical complications.

Introduction: In-office pharmacological sedation techniques are best applied to manage an extremely fearful preschooler, especially during primary dentition or a child’s early mixed dentition period. These should be used when non pharmacological behavioural management techniques fail either due to lack of communication or in children with special care needs. Aim: To compare the efficacy of oral administrations of midazolam, ketamine, combination of midazolam-ketamine (M+K) and nitrous oxide-oxygen (N2 O) inhalational sedation in achieving favorable behavioural outcome compared by using the Houpt scale in the treatment of anxious and uncooperative paediatric patients. Materials and Methods: A randomised clinical trial was conducted in the Department of Paediatric and Preventive Dentistry, SGT University, Haryana, India between September 2018 to December 2019. The study included 100 anxious children (Venham’s picture scale) aged three to five years, who required procedures under local anaesthesia administration were divided into four groups using envelop method. Each group was given either oral midazolam (M) (0.3 mg/kg) or oral ketamine (K) (3 mg/kg) or oral combination of midazolam+ketamine (M+K) (0.3 mg/kg and 2 mg/kg) or inhalational nitrous oxide-oxygen (N2 O). The behaviour response of the child was recorded using the Houpt scale. The oxygen saturation level and heart rate of each patient were also recorded before, after, and during the procedure. Adverse drug reactions post-treatment was also recorded. Analysis of Variance (ANOVA), Chi-square test and Mann-Whitney U test was used for statistical analysis. Results: The study comprised of 100 anxious children (mean age was 4.1±0.5 years) requiring administration of local anaesthesia with intent to complete in-office treatment. Statistically, a significant difference was found among behaviour outcomes of four groups (p-value=0.047). Acceptable behaviour was seen best in K+M group (88%), followed by oral ketamine (K) (68%), N2 O (59%), and oral midazolam (M) (52%). Adverse reactions were most commonly seen in the oral ketamine group. Conclusion: Oral M+K combination group is significantly better than oral ketamine (K), oral midazolam (M) or N2 O inhalation sedation to achieve the required behaviour for dental treatment in three to five years old patients.

Aim: We aimed to evaluate the prevalence of tobacco-associated oral mucosal lesions in Mahabubnagar district of Telangana state in South India. Methodology: A cross-sectional study was conducted in Mahabubnagar district for 6 months on 3200 subjects of both rural and urban people and the study was carried out by conducting camps at the Government Hospitals to assess the prevalence of oral mucosal lesions. People aged from 16 to 75 years, both men and women in same proportions, were included in the study. Results: 750 subjects had the habit of tobacco usage among a total of 3200 subjects. Among the 750 subjects, 225 (30.0%) subjects were being diagnosed with oral mucosal lesions. Of 225 subjects, 6 (2.67%) subjects had erythroplakia, 22 (9.78%) subjects had leukoplakia, 58 (25.78%) subjects had lichenoid reaction, 62 (27.56%) subjects had oral submucous fibrosis (OSMF), 45 (20.0%) subjects had palatal hyperkeratosis, and 32 (14.22%) subjects had tobacco pouch keratosis. Conclusion: From this study, we can conclude that prevalence of oral mucosal lesions was seen in tobacco-related oral habits where palatal hyperkeratosis was found among smokers; similarly OSMF was more among tobacco chewers and potentially malignant disorders were more prevalent in tobacco chewers than smokers.

Abstract Background In the current scenario, glass plays a vital contribution in our standard everyday life. Fractured and fragmented glasses are most commonly encountered at the crime scene. During the commission of the crime, glass breaks and shatters into fragments or into minute particles that serve as trace evidence and may provide a significant lead for the probe. The fracture of glass could be the consequence of an intentional act or unintentional act. For the forensic purpose, study of glass fractures, i.e., fractography has paramount importance as it can provide noteworthy data and encourages an assortment of assessments to investigate the case especially in the shooting cases where a firearm is used. Multiple fractures on a glass pane also have enough potential to establish an investigative link. Presently, air guns are being used in many of the cases due to their simple accessibility. There are a number of cases that have been reported that involved the use of air guns. Result This study was conducted to evaluate the pattern of multiple fractures on the glass by the air rifle. For this purpose, glass panes of various thicknesses were test fired perpendicularly at a fixed range with an air rifle having round nose pellet. Measurements and analysis were made on some fixed parameter. Data was analyzed graphically and statistically to check the consistency in the trends. Conclusion Consistency in the trends was observed, which is analyzed by the test for the goodness of fit. The findings of this work have provided some significant different perspectives that may effectively contribute to the criminal investigation.

For a small satellite, the processor onboard the attitude determination and control system (ADCS) is required to monitor, communicate, and control all the sensors and actuators. In addition, the processor is required to consistently communicate with the satellite bus. Consequently, the processor is unable to ensure all the sensors and actuators will immediately respond to the data acquisition request, which leads to asynchronous data problems. The extended Kalman filter (EKF) is commonly used in the attitude determination process, but it assumes fully synchronous data. The asynchronous data problem would greatly degrade the attitude determination accuracy by EKF. To minimize the attitude estimation accuracy loss due to asynchronous data while ensuring a reasonable computational complexity for small satellite applications, this paper proposes the simplex-back-propagation Kalman filter (SBPKF). The proposed SBPKF incorporates the time delay, gyro instability, and navigation error into both the measurement and covariance estimation during the Kalman update process. The performance of SBPKF has been compared with EKF, modified adaptive EKF (MAEKF), and moving–covariance Kalman filter (MC-KF). Simulation results show that the attitude estimation error of SBPKF is at least 30% better than EKF and MC-KF. In addition, the SBPKF’s computational complexity is 17% lower than MAEKF and 29% lower than MC-KF.

Neuropeptides are mainly secreted from the human central and peripheral nervous systems. Neuropeptides bind to its cognate rhodopsin-like G-protein coupled receptor (GPCR) and perform various physiological functions. Conventional cancer treatments in clinical practice still present many drawbacks due to the lack of selectivity toward the target cell, drug-resistance, and side-effects, thus pushing for the development of new therapeutic agents and therapies. Recent research suggests that neuropeptides influence cancer cell proliferation, invasion, metastasis, and angiogenesis and, therefore, they could be exploited as a target for novel anticancer therapies. Very recently, targeted approaches that inhibit neuropeptides and their associated receptors are being developed in cancer treatment. This review focuses on various neuropeptides and their potential utility as drug targets by different inhibitors as a recently identified approach to cancer prevention, with particular emphasis on colorectal cancer.

As robots become more advanced and capable, developing trust is an important factor of human-robot interaction and cooperation. However, as multiple environmental and social factors can influence trust, it is important to develop more elaborate scenarios and methods to measure human-robot trust. A widely used measurement of trust in social science is the investment game. In this study, we propose a scaled-up, immersive, science fiction Human-Robot Interaction (HRI) scenario for intrinsic motivation on human-robot collaboration, built upon the investment game and aimed at adapting the investment game for human-robot trust. For this purpose, we utilize two Neuro-Inspired COmpanion (NICO) - robots and a projected scenery. We investigate the applicability of our space mission experiment design to measure trust and the impact of non-verbal communication. We observe a correlation of 0.43 (p=0.02) between self-assessed trust and trust measured from the game, and a positive impact of non-verbal communication on trust (p=0.0008) and robot perception for anthropomorphism (p=0.007) and animacy (p=0.00002). We conclude that our scenario is an appropriate method to measure trust in human-robot interaction and also to study how non-verbal communication influences a human’s trust in robots.

Introduction: Caries pattern is multifactorial in context to the type of diet, tooth structure, time of insult, microflora and salivary contents (salivary pH, buffering action, salivary flow, etc.). Craniofacial relationship may be a contributing factor in the site of occurrence of caries i.e., mesial, distal, occlusal, palatal/lingual and buccal surfaces of primary and permanent molars. Aim: The aim of the study was to find out the effect of the type of malocclusion in primary dentition and mixed dentition period on the surface distribution of caries with respect to their molars along with overall DMFT (decayed, missing and filled teeth index) of the patient. Materials and Methods: A pilot study was conducted in Government and Private schools of district Gurugram, Haryana. Hundred children between 3-5 years of age with primary dentition and 8-10 years of age in mixed dentition period as per inclusion and exclusion criteria were included. Type of terminal plane relationship, according to Baume’s classification, i.e., Flush terminal/mesial step/distal step and affected carious site in all primary molars were examined in 3-5-year-old children. Similarly in 8-10-year-old, type of malocclusion according to Angle’s Classification and its association with carious sites in permanent first molar were examined. Decayed, missing and filled teeth index, DMFT/dmft (i.e., dmft=0-1, 1-2, ≤3 and DMFT+dmft (DMFT+dmft=0-1, 1-2, ≤3) was analysed in both groups, respectively. Results: The mesial step molar relationship was the most common malocclusion (93%) in primary dentition whereas in mixed dentition Angle’s Class I was the most common (84%) malocclusion. Caries occurrence was more in maxillary molars as compared to mandibular molars. The order of caries occurrence in primary and permanent dentition was occlusal surfaces>mesial surfaces>distal surfaces>buccal surfaces>palatal/lingual surfaces. The caries occurrence according to dmft index in primary dentition was not associated with any type of malocclusion, though it was more in mesial step molar relationship. Angle’s Class II malocclusion contributed significantly high DMFT+dmft index with p-value of 0.020. Conclusion: Type of malocclusion does not affect with surface pattern of caries on molars in primary and mixed dentition period. Decayed, missing and filled caries index may be significantly associated with Angle’s Class II malocclusion according to the present study.

Scientific examination of the physical evidence provides significant information beyond a reasonable doubt. Due to the increasing use of the glassy polymer i.e. polymethylmethacrylate instead of glass, the probability of the occurrence of the fractured polymethylmethacrylate sheet in a shooting incident cannot be ignored. Analysis of fracture pattern offers several analytical approaches that assist the forensic investigator. The use of air guns in criminal activities is increasing as well as these weapons have found to be fatal for living beings. This study was conducted to evaluate the fracture pattern on the polymethylmethacrylate by using an air rifle. The fracture pattern formed on polymethylmethacrylate sheets by the air guns shows some specific characteristics that may help to reconstruct the crime scene. The polymethylmethacrylate sheets were test-fired with Spring-Piston air rifles of .22″ (5.5 mm) and .177″ (4.5 mm). Data obtained from the measurements were then statistically analysed with the Chi-Square test. A consistency in hole diameter was observed. Analysis of fracture patterns may provide a lead to the investigator and may help to reconstruct a shooting incident. It can also distinguish between the standard firearm and air gun. The fracture on polymethylmethacrylate sheets gave significant findings that may efficaciously contribute to the forensic investigation of shooting incidences.

Various disease-associated forms or strains of α-synuclein (αSynD) can spread and accumulate in a prion-like fashion during synucleinopathies such as Parkinson’s disease (PD), Lewy body dementia (DLB), and multiple system atrophy (MSA). This capacity for self-propagation has enabled the development of seed amplification assays (SAAs) that can detect αSynD in clinical samples. Notably, α-synuclein real-time quaking-induced conversion (RT-QuIC) and protein misfolding cyclic amplification (PMCA) assays have evolved as ultrasensitive, specific, and relatively practical methods for detecting αSynD in a variety of biospecimens including brain tissue, CSF, skin, and olfactory mucosa from synucleinopathy patients. However, αSyn SAAs still lack concordance in detecting MSA and familial forms of PD/DLB, and the assay parameters show poor correlations with various clinical measures. End-point dilution analysis in αSyn RT-QuIC assays allows for the quantitation of relative amounts of αSynD seeding activity that may correlate moderately with clinical measures and levels of other biomarkers. Herein, we review recent advancements in α-synuclein SAAs for detecting αSynD and describe in detail the modified Spearman–Karber quantification algorithm used with end-point dilutions.

In the original article [...]

Psoriasis is a common immune-mediated disease resulting from altered cross-talk between keratinocytes and immune cells. Previous transcriptomic studies have identified thousands of deregulated genes in psoriasis skin; however, the transcriptomic changes confined to the epidermal compartment remained poorly characterized. The aim of this study was to characterize the transcriptomic landscape of psoriatic keratinocytes, using sorted CD45neg epidermal cells. Genes with functions in innate immunity, type I interferon response, cell cycle and keratinization were enriched among deregulated genes in psoriatic keratinocytes. Gene set enrichment analysis indicated the dominance of interleukin (IL)-22/IL-17A signatures in the epidermal psoriasis-signature. A set of deregulated genes overlapped with psoriasis-associated genetic regions, suggesting that genetic variations affecting gene expression in keratinocytes contribute to susceptibility to psoriasis. Several psoriasis-susceptibility genes, which were previously believed to be expressed preferentially or exclusively in immune cells, were identified as having altered expression in psoriatic keratinocytes. These results highlight the role of keratinocytes in the pathogenesis of psoriasis, and indicate that both genetic factors and an inflammatory microenvironment contribute to epidermal alterations in psoriasis.

Tofacitinib is a Janus kinase (JAK) inhibitor, which has shown efficacy in treating psoriasis. The mode of action of tofacitinib is not completely understood but it has been thought to be mediated by the inhibition of CD4+ T-cell activation. Here, we investigated whether the molecular targets of tofacitinib are expressed in keratinocytes, and whether tofacitinib can modulate the activity of the JAK/Signal Transducer and Activators of Transcription (STAT)-pathway in keratinocytes. Transcriptomic profiling of human keratinocytes treated with IL-22 in combination with tofacitinib revealed that tofacitinib could prevent the majority of IL-22-mediated gene expression changes. Pathway analysis of tofacitinib-regulated genes in keratinocytes revealed enrichment of genes involved in the JAK/STAT signalling pathway. Quantitative real-time-PCR confirmed the upregulation of S100A7 and downregulation of EGR1 expression by IL-22, which was prevented by tofacitinib pre-treatment. These results indicate a direct effect of tofacinitib on keratinocytes, which can have relevance for systemic as well as for topical treatment of psoriasis with tofacitinib.

Gold nanoparticles (AuNPs) have been widely explored and are well-known for their medical applications. Chemical and physical synthesis methods are a way to make AuNPs. In any case, the hunt for other more ecologically friendly and cost-effective large-scale technologies, such as environmentally friendly biological processes known as green synthesis, has been gaining interest by worldwide researchers. The international focus on green nanotechnology research has resulted in various nanomaterials being used in environmentally and physiologically acceptable applications. Several advantages over conventional physical and chemical synthesis (simple, one-step approach to synthesize, cost-effectiveness, energy efficiency, and biocompatibility) have drawn scientists’ attention to exploring the green synthesis of AuNPs by exploiting plants’ secondary metabolites. Biogenic approaches, mainly the plant-based synthesis of metal nanoparticles, have been chosen as the ideal strategy due to their environmental and in vivo safety, as well as their ease of synthesis. In this review, we reviewed the use of green synthesized AuNPs in the treatment of cancer by utilizing phytochemicals found in plant extracts. This article reviews plant-based methods for producing AuNPs, characterization methods of synthesized AuNPs, and discusses their physiochemical properties. This study also discusses recent breakthroughs and achievements in using green synthesized AuNPs in cancer treatment and different mechanisms of action, such as reactive oxygen species (ROS), mediated mitochondrial dysfunction and caspase activation, leading to apoptosis, etc., for their anticancer and cytotoxic effects. Understanding the mechanisms underlying AuNPs therapeutic efficacy will aid in developing personalized medicines and treatments for cancer as a potential cancer therapeutic strategy.

Emergence of Amphotericin B (AmB) resistant Leishmania donovani has posed major therapeutic challenge against the parasite. Consequently, combination therapy aimed at multiple molecular targets, based on proteome wise network analysis has been recommended. In this regard we had earlier identified and proposed L-asparaginase of Leishmania donovani (LdAI) as a crucial metabolic target. Here we report that both LdAI overexpressing axenic amastigote and promastigote forms of L. donovani survives better when challenged with AmB as compared to wild type strain. Conversely, qRT-PCR analysis showed an upregulation of LdAI in both forms upon AmB treatment. Our data demonstrates the importance of LdAI in imparting immediate protective response to the parasite upon AmB treatment. In the absence of structural and functional information, we modeled LdAI and validated its solution structure through small angle X-ray scattering (SAXS) analysis. We identified its specific inhibitors through ligand and structure-based approach and characterized their effects on enzymatic properties (Km, Vmax, Kcat) of LdAI. We show that in presence of two of the inhibitors L1 and L2, the survival of L. donovani is compromised whereas overexpression of LdAI in these cells restores viability. Taken together, our results conclusively prove that LdAI is a crucial metabolic enzyme conferring early counter measure against AmB treatment by Leishmania. Keywords: Leishmania donovani, L-asparaginase, Amphotericin B resistance, Metabolic target

Abstract Background Glass is the hard, amorphous solid. Glass fragments may be an evidence of great value encountered in the investigation of various types of offences. At the scene of occurrence, the glass may be fractured either as an intentional act or due to accident. Glass fractures are of paramount importance in shooting cases where firearm is used as it can provide significant information related to the occurrence and facilitates a variety of evaluations. In fact, fractography i.e. analysis of fracture pattern, is the means and methods for characterization of fractured units or fragments in order to study or identify the mechanism of such fractures. The study of fracture pattern of glass has been of long interest to the forensic community. The glass fracture pattern analysis is very useful to establish the sequence of events and to link together items of evidence and it is of paramount importance in such cases where firearm is used. Now, the use of air guns in criminal activities is an alarm to the law enforcement agencies. The main objective of this work is to analyze the pattern of the fractures on windowpane of various thicknesses with regular .177″/ 4.5 mm lead pellet fired through the .177″/ 4.5 mm caliber Air Rifle manufactured in India. The window panes were kept at front, perpendicularly and away at a fixed distance from the muzzle end of Air Rifle. Samples were measured and analyzed on some fixed parameters. To analyze the consistency, measurements were analyzed graphically and statically checked for the goodness of fit (Chi-Square Test). Result The graphical representation of the measurements of different samples shows regularity in the features and Chi Square test gives very significant information regarding the consistency. Conclusion The hole diameter is ranging from 4.77 to 7.5 mm in case of air rifle. It can lead to distinguish the weapon by which fracture was made, whether it is standard or air weapon. The outcomes of this work on the windowpane by .177″/4.5 mm air rifles may be efficacious to forensic community.

The microstructural influence on hydrogen permeation and trapping in pure iron and two ferritic-pearlitic steels, AISI 1018 and AISI 4340 is quantified. To this end, hydrogen is introduced into specimens of these materials through electrochemical charging and the total hydrogen content of the specimens are quantified following gas fusion analysis principle. Furthermore, a modeling framework based on Fickian diffusion equations including the relevant microstructural features, electrochemical charging conditions and three-dimensional geometry of the specimen affecting the overall diffusion behavior is adopted to describe the time-dependence of hydrogen content in the three materials. The approach quantitatively describes the hydrogen ingress into the three materials, as well as its distribution across various defects and microstructural features. Traps of two potencies are identified, dislocations and grain boundaries (trap 1), and ferrite/cementite interfaces (trap 2). The former are shown to be responsible for the trapped hydrogen at early stages of its ingress, whereas trap 2 is shown to gather trapped hydrogen at later stages. The ability to design microstructures to control hydrogen ingress and diffusion is discussed, showing how the framework presented here can be adopted for controlling hydrogen in commercial components, and how this can delay hydrogen-related embrittlement. Keywords: Hydrogen diffusion, Hydrogen quantification, Hydrogen embrittlement, Steels, Microstructure, Modeling

Over the last decade, there has been a paradigm shift away from labor-intensive and time-consuming materials discovery methods, and materials exploration through informatics approaches is gaining traction at present. Current approaches are typically centered around the idea of achieving this exploration through high-throughput (HT) experimentation/computation. Such approaches, however, do not account for the practicalities of resource constraints which eventually result in bottlenecks at various stage of the workflow. Regardless of how many bottlenecks are eliminated, the fact that ultimately a human must make decisions about what to do with the acquired information implies that HT frameworks face hard limits that will be extremely difficult to overcome. Recently, this problem has been addressed by framing the materials discovery process as an optimal experiment design problem. In this article, we discuss the need for optimal experiment design, the challenges in it's implementation and finally discuss some successful examples of materials discovery via experiment design.

Herein, we correlate the prior austenite grain (PAG) microstructure to deformation and fracture mechanisms of an ultra-high strength martensitic steel. To this end, a low-carbon martensitic steel is subjected to five heat-treatments and the PAG microstructure in the material is reconstructed from the EBSD inverse pole figure maps of the martensitic microstructure. The deformation and fracture response of all heat-treated materials are characterized by in situ tension tests of dog-bone and single-edge notch specimens that allow us to capture both the macroscopic mechanical response and the evolution of microscopic strains via microscale digital image correlation. The experimental results, together with microstructure-based finite element analysis, are then used to elucidate the effect of the PAG microstructure on the mechanical response of the material. Our results show that the interaction between the heterogeneous deformation fields induced by the notch and the bimodal PAG size distribution leads to an increase in the propensity of shear deformation and degradation in the fracture response of the material with increasing heat-treatment temperature and time. Our results also suggest that achieving a unform distribution of fine grains is an effective way to enhance both the strength and fracture properties of this class of materials.

Advanced high strength dual-phase steels are one of the most widely sought-after structural materials for automotive applications. These high strength steels, however, are prone to fracture under bending-dominated manufacturing processes. Experimental observations suggest that the bendability of these steels is sensitive to the presence of subsurface non-metallic inclusions and the inclusions exhibit a rather discrete size effect on the bendability of these steels. Following this, we have carried out a series of microstructure-based finite element calculations of ductile fracture in an advanced high strength dual-phase steel under bending. In the calculations, both the dual-phase microstructure and inclusion are discretely modeled. To gain additional insight, we have also analyzed the effect of an inclusion on the bendability of a single-phase material. In line with the experimental observations, strong inclusion size effect on the bendability of the dual-phase steel naturally emerge in the calculations. Furthermore, supervised machine learning is used to quantify the effects of the multivariable input space associated with the dual-phase microstructure and inclusion on the bendability of the steel. The results of the supervised machine learning are then used to identify the contributions of individual features and isolate critical features that control the bendability of dual-phase steels.

Lightweight materials with high strength are desirable for applications where they could reduce energy consumption. Here, the authors develop a low cost beta-titanium alloy that uses a hierarchical nanostructure of precipitates with different sizes to achieve high strength.

BACKGROUND: Lecturing (didactic) has been the key teaching-learning method for a long time. As per competency-based medical education, an Indian medical graduate should be competent in recommended skills. In the subject of Community Medicine of medical undergraduation, “Biostatistics” is one of the components of the curriculum. Often the students find the statistics challenging to understand and thus neglect it or prefer rote learning. In the recent era, many newer teaching-learning modalities have come up, namely problem-based learning (PBL), small group teaching, community-based learning, etc. The objective was to compare the utility and effectiveness of PBL versus traditional teaching techniques (didactic) for Biostatistics. MATERIALS AND METHODS: The study was conducted in the department of Community Medicine, Government Medical College, Azamgarh (Uttar Pradesh) from March to November 2019. A total of 96 medical students of the final year were randomly divided into two groups. 'Group A' underwent didactic lecturing whereas “Group B” had problem-based learning for identified topics in Biostatistics. The teaching material and instructors were the same for both groups. Two weeks after completion of sessions, students' assessment was carried out for both groups. RESULTS: The study demonstrated that the PBL method was a more effective way of teaching-learning statistics compared to didactic lecturing. A significant difference (P < 0.05) was observed between the mean examination score of Group A (traditional teaching technique) and Group B (PBL). Group B had higher scores than group A in all assessment heads (Objective, Descriptive, and Viva-voce). PBL was perceived to be a student-centric Teaching-learning method promoting analytical skills, critical thinking & overall self-directed learning. CONCLUSION: PBL teaching method was found to be effective in improving the students' performance in Statistics in comparison to didactic lecturing.

In this paper, we review the recent advances which have taken place in the understanding and applications of acoustic/elastic metamaterials. Metamaterials are artificially created composite materials which exhibit unusual properties that are not found in nature. We begin with presenting arguments from discrete systems which support the case for the existence of unusual material properties such as tensorial and/or negative density. The arguments are then extended to elastic continuums through coherent averaging principles. The resulting coupled and nonlocal homogenized relations, called the Willis relations, are presented as the natural description of inhomogeneous elastodynamics. They are specialized to Bloch waves propagating in periodic composites and we show that the Willis properties display the unusual behavior which is often required in metamaterial applications such as the Veselago lens. We finally present the recent advances in the area of transformation elastodynamics, charting its inspirations from transformation optics, clarifying its particular challenges, and identifying its connection with the constitutive relations of the Willis and the Cosserat types.

Introduction: Teas is known for its anticariogenic properties and various mechanisms have been invoked to explain this effect. One such proposed mechanism is inhibition of salivary alpha amylase activity by endogenous tannins present in tea. Aim: The objective of the present study was to determine whether or not the ingestion of black tea decoction inhibits the enzyme salivary amylase and thus interferes with the release of maltose from intraoral entrapped particles of food. Materials and Methods: A total of 30 children in the age group of 12 - 15 years were selected for the study. After two hours of fasting subjects consumed two salted crackers for 60 second following which they rinsed with water (control solution) and then with 1.5% black tea decoction (test solution) next day. Retained food particles were recovered from buccal aspect of left mandibular premolar and salivary amylase activity was noted via chromatography. Paired t-test was applied for statistical analysis. Results: Maltose to Sucrose ratio was used to evaluate the result. The average ratio was 3.27 for control solution and 1.82 for test solution. The results were statistically highly significant (p

Dharmendra K Yadav, Abha Meena, Ankit Srivastava, D Chanda, Feroz Khan, SK ChattopadhyayMetabolic and Structural Biology Department, Central Institute of Medicinal and Aromatic Plants, Council of Scientific and Industrial Research, PO-CIMAP, IndiaAbstract: Immunomodulation is the process of alteration in immune response due to foreign intrusion of molecules inside the body. Along with the available drugs, a large number of herbal drugs are promoted in traditional Indian treatments, for their immunomodulating activity. Natural coumarinolignoids isolated from the seeds of Cleome viscose have been recognized as having hepatoprotective action and have recently been tested preclinically for their immunomodulatory activity affecting both cell-mediated and humoral immune response. To explore the immunomodulatory compound from derivatives of coumarinolignoids, a quantitative structure activity relationship (QSAR) and molecular docking studies were performed. Theoretical results are in accord with the in vivo experimental data studied on Swiss albino mice. Immunostimulatory activity was predicted through QSAR model, developed by forward feed multiple linear regression method with leave-one-out approach. Relationship correlating measure of QSAR model was 99% (R2 = 0.99) and predictive accuracy was 96% (RCV2 = 0.96). QSAR studies indicate that dipole moment, steric energy, amide group count, lambda max (UV-visible), and molar refractivity correlates well with biological activity, while decrease in dipole moment, steric energy, and molar refractivity has negative correlation. Docking studies also showed strong binding affinity to immunomodulatory receptors.Keywords: coumarinolignoids, immunomodulation, docking, QSAR, regression model

Small molecule based therapeutic intervention of amyloids has been limited by their low solubility and poor pharmacokinetic characteristics. We report here, the use of water soluble poly lactic-co-glycolic acid (PLGA)-encapsulated curcumin and emetine nanoparticles (Cm-NPs and Em-NPs, respectively), as potential modulators of gelsolin amyloidogenesis. Using the amyloid-specific dye Thioflavin T (ThT) as an indicator along with electron microscopic imaging we show that the presence of Cm-NPs augmented amyloid formation in gelsolin by skipping the pre-fibrillar assemblies, while Em-NPs induced non-fibrillar aggregates. These two types of aggregates differed in their morphologies, surface hydrophobicity and secondary structural signatures, confirming that they followed distinct pathways. In spite of differences, both these aggregates displayed reduced toxicity against SH-SY5Y human neuroblastoma cells as compared to control gelsolin amyloids. We conclude that the cytotoxicity of gelsolin amyloids can be reduced by either stalling or accelerating its fibrillation process. In addition, Cm-NPs increased the fibrillar bulk while Em-NPs defibrillated the pre-formed gelsolin amyloids. Moreover, amyloid modulation happened at a much lower concentration and at a faster rate by the PLGA encapsulated compounds as compared to their free forms. Thus, besides improving pharmacokinetic and biocompatible properties of curcumin and emetine, PLGA conjugation elevates the therapeutic potential of both small molecules against amyloid fibrillation and toxicity.

We report the results of the calculation of negative effective density and negative effective compliance for a layered composite. We show that the frequency-dependent effective properties remain positive for cases which lack the possibility of localized resonances (a 2-phase composite) whereas they may become negative for cases where there exists a possibility of local resonance below the length-scale of the wavelength (a 3-phase composite). We also show that the introduction of damping in the system considerably affects the effective properties in the frequency region close to the resonance. It is envisaged that this demonstration of doubly negative material characteristics for 1-D wave propagation would pave the way for the design and synthesis of doubly negative material response for full 3-D elastic wave propagation.